The clinical success of cancer immune checkpoint blockade(ICB)has refocused attention on tumor-infiltrating lymphocytes(TILs)across cancer types.The outcome of immune checkpoint inhibitor therapy in cancer patients ha...The clinical success of cancer immune checkpoint blockade(ICB)has refocused attention on tumor-infiltrating lymphocytes(TILs)across cancer types.The outcome of immune checkpoint inhibitor therapy in cancer patients has been linked to the quality and magnitude of T cell,NK cell,and more recently,B cell responses within the tumor microenvironment.State-of-the-art single-cell analysis of TIL gene expression profiles and clonality has revealed a remarkable degree of cellular heterogeneity and distinct patterns of immune activation and exhaustion.Many of these states are conserved across tumor types,in line with the broad responses observed clinically.Despite this homology,not all cancer types with similar TIL landscapes respond similarly to immunotherapy,highlighting the complexity of the underlying tumor-immune interactions.This observation is further confounded by the strong prognostic benefit of TILs observed for tumor types that have so far respond poorly to immunotherapy.Thus,while a holistic view of lymphocyte infiltration and dysfunction on a single-cell level is emerging,the search for response and prognostic biomarkers is just beginning.Within this review,we discuss recent advances in the understanding of TIL biology,their prognostic benefit,and their predictive value for therapy.展开更多
Inflammatory bowel disease (IBD) results from a complex series of interactions between susceptibility genes, the environment, and the immune system. The host microbiome, as well as viruses and fungi, play important ro...Inflammatory bowel disease (IBD) results from a complex series of interactions between susceptibility genes, the environment, and the immune system. The host microbiome, as well as viruses and fungi, play important roles in the development of IBD either by causing inflammation directly or indirectly through an altered immune system. New technologies have allowed researchers to be able to quantify the various components of the microbiome, which will allow for future developments in the etiology of IBD. Various components of the mucosal immune system are implicated in the pathogenesis of IBD and include intestinal epithelial cells, innate lymphoid cells, cells of the innate (macrophages/monocytes, neutrophils, and dendritic cells) and adaptive (T-cells and B-cells) immune system, and their secreted mediators (cytokines and chemokines). Either a mucosal susceptibility or defect in sampling of gut luminal antigen, possibly through the process of autophagy, leads to activation of innate immune response that may be mediated by enhanced toll-like receptor activity. The antigen presenting cells then mediate the differentiation of naïve T-cells into effector T helper (Th) cells, including Th1, Th2, and Th17, which alter gut homeostasis and lead to IBD. In this review, the effects of these components in the immunopathogenesis of IBD will be discussed.展开更多
AIM: To report 3 of 120 patients on the German MALT lymphoma trial with H. pylori associated gastric MALT lymphoma who developed early gastric cancer 4 and 5 years, after complete lymphoma remission following cure of ...AIM: To report 3 of 120 patients on the German MALT lymphoma trial with H. pylori associated gastric MALT lymphoma who developed early gastric cancer 4 and 5 years, after complete lymphoma remission following cure of H. pylori infection. PATIENTS AND RESULTS: Three patients (two men, 74 and 70 years; one women, 77 years) with H. pylori-associated low-grade MALT lymphoma achieved complete lymphoma remission after being cured. Surveillance endoscopies were performed twice a year in accordance to the protocol. Four years after complete lymphoma remission in two patients, and after 5 years in the other, early gastric adenocarcinoma of the mucosa-type, type IIa and type IIc, respectively, was detected, which were completely removed by endoscopic mucosa resection. In one patient, the gastric cancer was diagnosed at the same location as the previous MALT lymphoma, in the other patients it was detected at different sites of the stomach distant from location of the previous MALT lymphoma. The patients were H. pylori negative during the whole follow-up time. CONCLUSION: These findings strengthen the importance of regular Long-term follow-up endoscopies in patients with complete remission of gastric MALT lymphoma after cure of H. pylori infection. Furthermore, gastric adenocarcinoma may develop despite eradication of H. pylori.展开更多
Background Pulmonary mucosa-associated lymphoid tissue （MALT） lymphoma is the most frequent type of non-Hodgkin＇s lymphoma （NHL） that primarily involves the lungs. It represents a rare entity accounting for less ...Background Pulmonary mucosa-associated lymphoid tissue （MALT） lymphoma is the most frequent type of non-Hodgkin＇s lymphoma （NHL） that primarily involves the lungs. It represents a rare entity accounting for less than 1% of all NHLs and the clinical features have yet to be clearly elucidated.展开更多
Innate sensing of pathogens by pattern-recognition receptors （PRRs） plays essential roles in the innate discrimination between self and non-self components, leading to the generation of innate immune defense and inf...Innate sensing of pathogens by pattern-recognition receptors （PRRs） plays essential roles in the innate discrimination between self and non-self components, leading to the generation of innate immune defense and inflammatory responses. The initiation, activation and resolution of innate inflammatory response are mediated by a complex network of interactions among the numerous cellular and molecular components of immune and non- immune system. While a controlled and beneficial innate inflammatory response is critical for the elimination of pathogens and maintenance of tissue homeostasis, dysregulated or sustained inflammation leads to pathological conditions such as chronic infection, inflammatory autoimmune diseases. In this review, we discuss some of the recent advances in our understanding of the cellular and molecular mechanisms for the establishment and reJzulation of innate immunity and inflammatory responses.展开更多
The stomach is the most frequently involved site for extranodal lymphomas,accounting for nearly two-thirds of all gastrointestinal cases.It is widely accepted that gastric B-cell,low-grade mucosal-associated lymphoid ...The stomach is the most frequently involved site for extranodal lymphomas,accounting for nearly two-thirds of all gastrointestinal cases.It is widely accepted that gastric B-cell,low-grade mucosal-associated lymphoid tissue(MALT)-lymphoma is caused by Helicobacter pylori(H.pylori)infection.MALT-lymphomas may engender different clinical and endoscopic patterns.Often,diagnosis is confirmed in patients with only vague dyspeptic symptoms and without macroscopic lesions on gastric mucosa.H.pylori eradication leads to lymphoma remission in a large number of patients when treatment occurs at an early stage(Ⅰ-Ⅱ1).Neoplasia confined to the submucosa,localized in the antral region of the stomach,and without API2-MALT1 translocation,shows a high probability of remission following H.pylori eradication.When both bacterial infection and lymphoma recur,further eradication therapy is generally effective.Radiotherapy,chemotherapy and,in selected cases,surgery are the available therapeutic options with a high success rate for those patients who fail to achieve remission,while data on immunotherapy with monoclonal antibodies (rituximab)are still scarce.The 5-year survival rate is higher than 90%,but careful,long-term follow-up is required in these patients since lymphoma recurrence has been reported in some cases.展开更多
The type 2 immune response is critical for host defense against large parasites such as helminths.On the other hand,dysregulation of the type 2 immune response may cause immunopathological conditions,including asthma,...The type 2 immune response is critical for host defense against large parasites such as helminths.On the other hand,dysregulation of the type 2 immune response may cause immunopathological conditions,including asthma,atopic dermatitis,rhinitis,and anaphylaxis.Thus,a balanced type 2 immune response must be achieved to mount effective protection against invading pathogens while avoiding immunopathology.The classical model of type 2 immunity mainly involves the differentiation of type 2 T helper(Th2)cells and the production of distinct type 2 cytokines,including interleukin-4(IL-4),IL-5,and IL-13.Group 2 innate lymphoid cells(ILC2s)were recently recognized as another important source of type 2 cytokines.Although eosinophils,mast cells,and basophils can also express type 2 cytokines and participate in type 2 immune responses to various degrees,the production of type 2 cytokines by the lymphoid lineages,Th2 cells,and ILC2s in particular is the central event during the type 2 immune response.In this review,we discuss recent advances in our understanding of how ILC2s and Th2 cells orchestrate type 2 immune responses through direct and indirect interactions.展开更多
A mounting body of evidence indicates that dietary fiber(DF)metabolites produced by commensal bacteria play essential roles in balancing the immune system.DF,considered nonessential nutrients in the past,is now consid...A mounting body of evidence indicates that dietary fiber(DF)metabolites produced by commensal bacteria play essential roles in balancing the immune system.DF,considered nonessential nutrients in the past,is now considered to be necessary to maintain adequate levels of immunity and suppress inflammatory and allergic responses.Short-chain fatty acids(SCFAs),such as acetate,propionate,and butyrate,are the major DF metabolites and mostly produced by specialized commensal bacteria that are capable of breaking down DF into simpler saccharides and further metabolizing the saccharides into SCFAs.SCFAs act on many cell types to regulate a number of important biological processes,including host metabolism,intestinal functions,and immunity system.This review specifically highlights the regulatory functions of DF and SCFAs in the immune system with a focus on major innate and adaptive lymphocytes.Current information regarding how SCFAs regulate innate lymphoid cells,T helper cells,cytotoxic T cells,and B cells and how these functions impact immunity,inflammation,and allergic responses are discussed.展开更多
Cell-based immunotherapy for lymphoid malignancies has gained increasing attention as patients develop resistance to conventional treatments.cd T cells,which have major histocompatibility complex(MHC)-unrestricted lyt...Cell-based immunotherapy for lymphoid malignancies has gained increasing attention as patients develop resistance to conventional treatments.cd T cells,which have major histocompatibility complex(MHC)-unrestricted lytic activity,have become a promising candidate population for adoptive cell transfer therapy.We previously established a stable condition for expanding cd T cells by using anti-cd T-cell receptor(TCR)antibody.In this study,we found that adoptive transfer of the expanded cd T cells to Daudi lymphoma-bearing nude mice significantly prolonged the survival time of the mice and improved their living status.We further investigated the characteristics of these antibody-expanded cd T cells compared to the more commonly used phosphoantigen-expanded cd T cells and evaluated the feasibility of employing them in the treatment of lymphoid malignancies.Slow but sustained proliferation of human peripheral blood cd T cells was observed upon stimulation with anti-cd TCR antibody.Compared to phosphoantigen-stimulated cd T cells,the antibody-expanded cells manifested similar functional phenotypes and cytotoxic activity towards lymphoma cell lines.It is noteworthy that the anti-cd TCR antibody could expand both the Vd1 and Vd2 subsets of cd T cells.The in vitro-expanded Vd1 T cells displayed comparable tumour cell-killing activity to Vd2 T cells.Importantly,owing to higher C–C chemokine receptor 4(CCR4)and CCR8 expression,the Vd1 T cells were more prone to infiltrate CCL17-or CCL22-expressing lymphomas than the Vd2 T cells.Characterizing the peripheral blood cd T cells from lymphoma patients further confirmed that the anti-cd TCR antibody-expanded cd T cells could be a more efficacious choice for the treatment of lymphoid malignancies than phosphoantigen-expanded cd T cells.展开更多
Accumulating evidence suggests that ketogenic diets(KDs)mediate the rise of circulating ketone bodies and exert a potential antiinflammatory effect;however,the consequences of this unique diet on colitis remain unknow...Accumulating evidence suggests that ketogenic diets(KDs)mediate the rise of circulating ketone bodies and exert a potential antiinflammatory effect;however,the consequences of this unique diet on colitis remain unknown.We performed a series of systematic studies using a dextran sulfate sodium(DSS)animal model of inflammatory colitis.Animals were fed with a KD,low-carbohydrate diet(LCD),or normal diet(ND).Germ-free mice were utilized in validation experiments.Colon tissues were analyzed by transcriptome sequencing,RT2 profiler PCR array,histopathology,and immunofluorescence.Serum samples were analyzed by metabolic assay kit.Fecal samples were analyzed by 16S rRNA gene sequencing,liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry.We observed that KD alleviated colitis by altering the gut microbiota and metabolites in a manner distinct from LCD.Quantitative diet experiments confirmed the unique impact of KD relative to LCD with a reproducible increase in Akkermansia,whereas the opposite was observed for Escherichia/Shigella.After colitis induction,the KD protected intestinal barrier function,and reduced the production of R0Ryt+CD3_group 3 innate lymphoid cells(ILC3s)and related inflammatory cytokines(IL-17a,IL-18,IL-22,Ccl4).Finally,fecal microbiota transplantation into germ-free mice revealed that the KD-mediated colitis inhibition and ILC3 regulation were dependent on the modification of gut microbiota.Taken together,our study presents a global view of microbiome-metabolomics changes that occur during KD colitis treatment,and identifies the regulation of gut microbiome and ILC3s as novel targets involving in IBD dietary therapy.展开更多
AIM: To investigate treatment outcome of Helicobacter pylori (H.pylori )-negative low-grade gastric mucosaassociated lymphoid tissue (MALT) lymphoma.METHODS: In this study,we retrospectively reviewed the clinical outc...AIM: To investigate treatment outcome of Helicobacter pylori (H.pylori )-negative low-grade gastric mucosaassociated lymphoid tissue (MALT) lymphoma.METHODS: In this study,we retrospectively reviewed the clinical outcome and clinicopathologic factors of stage Ⅰ E H.pylori -negative low-grade gastric MALT lymphoma cases from August 1998 to June 2009.RESULTS: A total of eleven patients with H.pylori -negative low-grade gastric MALT lymphoma were enrolled in the study and received anti-H.pylori eradication treatment and/or radiotherapy or excisional therapy.Complete remission (CR) of gastric MALT lymphoma was achieved in all patients.The time to CR was 1-66 mo (median,1 mo).CONCLUSION: Eradication therapy may be offered as an initial treatment option even in cases of localized H.pylori -negative gastric MALT lymphoma.展开更多
Natural killer(NK)cells are innate lymphoid cells endowed with cytolytic activity and a capacity to secrete cytokines and chemokines.Several lines of evidence suggest that NK cells play an important role in anti-tumor...Natural killer(NK)cells are innate lymphoid cells endowed with cytolytic activity and a capacity to secrete cytokines and chemokines.Several lines of evidence suggest that NK cells play an important role in anti-tumor immunity.Some therapies against hematological malignacies make use of the immune properties of NK cells,such as their ability to kill residual leukemic blasts efficiently after conditioning during haploidentical hematopoietic stem cell transplantation.However,knowledge on NK cell infiltration and the status of NK cell responsiveness in solid tumors is limited so far.The pro-angiogenic role of the recently described NK cell-like type 1 innate lymphoid cells(ILC1s)and their phenotypic resemblance to NK cells are confounding factors that add a level of complexity,at least in mice.Here,we review the current knowledge on the presence and function of NK cells in solid tumors as well as the immunotherapeutic approaches designed to harness NK cell functions in these conditions,including those that aim to reinforce conventional anti-tumor therapies to increase the chances of successful treatment.展开更多
The intestine and the gut-associated lymphoid tissue（GALT） are essential components of whole body immune defense,protecting the body from foreign antigens and pathogens,while allowing tolerance to commensal bacteria...The intestine and the gut-associated lymphoid tissue（GALT） are essential components of whole body immune defense,protecting the body from foreign antigens and pathogens,while allowing tolerance to commensal bacteria and dietary antigens.The requirement for protein to support the immune system is well established.Less is known regarding the immune modifying properties of individual amino acids,particularly on the GALT.Both oral and parenteral feeding studies have established convincing evidence that not only the total protein intake,but the availability of specific dietary amino acids（in particular glutamine,glutamate,and arginine,and perhaps methionine,cysteine and threonine） are essential to optimizing the immune functions of the intestine and the proximal resident immune cells.These amino acids each have unique properties that include,maintaining the integrity,growth and function of the intestine,as well as normalizing inflammatory cytokine secretion and improving T-lymphocyte numbers,specific T cell functions,and the secretion of IgA by lamina propria cells.Our understanding of this area has come from studies that have supplemented single amino acids to a mixed protein diet and measuring the effect on specific immune parameters.Future studies should be designed using amino acid mixtures that target a number of specific functions of GALT in order to optimize immune function in domestic animals and humans during critical periods of development and various disease states.展开更多
Gastrointestinal lymphoma is the most common type of extranodal lymphoma,and most commonly affects the stomach.Marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue(MALT)and diffuse large B-cell lymph...Gastrointestinal lymphoma is the most common type of extranodal lymphoma,and most commonly affects the stomach.Marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue(MALT)and diffuse large B-cell lymphoma are the most common histologic types of gastric lymphoma.Despite its increasing incidence,diagnosis of gastric lymphoma is difficult at an earlier stage due to its nonspecific symptoms and endoscopic findings,and,thus,a high index of suspicion,and multiple,deep,repeated biopsies at abnormally and normally appearing sites in the stomach are needed.In addition,testing for Helicobacter pylori(H.pylori)infection and endoscopic ultrasonography to determine the depth of tumor invasion and involvement of regional lymph nodes is essential for predicting response to H.pylori eradication and for assessment of disease progression.In addition,H.pylori infection and MALT lymphoma development are associated,and complete regression of low-grade MALT lymphomas after H.pylori eradication has been demonstrated.Radiotherapy and/or chemotherapy can be used in cases that show poor response to H.pylori eradication,negativity for H.pylori infection,or high-grade lymphoma.展开更多
Tertiary lymphoid structures(TLS)are ectopic lymphoid structures in cancers that are largely associated with favourable prognosis.However,the prognostic value of TLSs in oral squamous cell carcinoma(OSCC)is largely un...Tertiary lymphoid structures(TLS)are ectopic lymphoid structures in cancers that are largely associated with favourable prognosis.However,the prognostic value of TLSs in oral squamous cell carcinoma(OSCC)is largely unknown,and the association between tumour infiltrating lymphocytes(TILs)and TLSs has been rarely explored in OSCC.In this study,associated markers of TLS,including peripheral node address(PNAd)in high endothelial venules,CD20 in B cells and CD3 in T cells,were examined in 168 OSCC patients,and survival analysis was performed between TLS-positive and TLS-negative cohorts.We detected the presence of TILs by staining CD8+cytotoxic T cells and CD57+NK cells as well.TLSs appeared as highly organized structures in 45(26.8%)cases.TLSpositive patients had a better 5-year overall survival(OS)rate(88.9%vs.56.1%,P<0.001)and relapse-free survival(RFS)rate(88.9%vs.63.4%,P=0.002).Moreover,the presence of TLS was an independent prognostic factor for both the 5-year OS rate(hazard ratio[HR]=3.784;95%confidence interval[CI],1.498–9.562)and RFS rate(HR=3.296;95%CI,1.279–8.490)in multivariate analysis.Furthermore,a higher density of CD8+T cells and CD57+NK cells was found in TLS-positive sections than in TLS-negative counterparts(P<0.001),and their combination provided a higher predictive accuracy(AUC=0.730;95%CI,0.654–0.805).In conclusion,our results suggest that TLS is an independent positive prognostic factor for OSCC patients.These findings provide a theoretical basis for the future diagnostic and therapeutic value of TLSs in OSCC treatment.展开更多
文摘The clinical success of cancer immune checkpoint blockade(ICB)has refocused attention on tumor-infiltrating lymphocytes(TILs)across cancer types.The outcome of immune checkpoint inhibitor therapy in cancer patients has been linked to the quality and magnitude of T cell,NK cell,and more recently,B cell responses within the tumor microenvironment.State-of-the-art single-cell analysis of TIL gene expression profiles and clonality has revealed a remarkable degree of cellular heterogeneity and distinct patterns of immune activation and exhaustion.Many of these states are conserved across tumor types,in line with the broad responses observed clinically.Despite this homology,not all cancer types with similar TIL landscapes respond similarly to immunotherapy,highlighting the complexity of the underlying tumor-immune interactions.This observation is further confounded by the strong prognostic benefit of TILs observed for tumor types that have so far respond poorly to immunotherapy.Thus,while a holistic view of lymphocyte infiltration and dysfunction on a single-cell level is emerging,the search for response and prognostic biomarkers is just beginning.Within this review,we discuss recent advances in the understanding of TIL biology,their prognostic benefit,and their predictive value for therapy.
基金Supported by NIH KO8 DK093578CCFA Career Development Award 3467(DQS)F Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute
文摘Inflammatory bowel disease (IBD) results from a complex series of interactions between susceptibility genes, the environment, and the immune system. The host microbiome, as well as viruses and fungi, play important roles in the development of IBD either by causing inflammation directly or indirectly through an altered immune system. New technologies have allowed researchers to be able to quantify the various components of the microbiome, which will allow for future developments in the etiology of IBD. Various components of the mucosal immune system are implicated in the pathogenesis of IBD and include intestinal epithelial cells, innate lymphoid cells, cells of the innate (macrophages/monocytes, neutrophils, and dendritic cells) and adaptive (T-cells and B-cells) immune system, and their secreted mediators (cytokines and chemokines). Either a mucosal susceptibility or defect in sampling of gut luminal antigen, possibly through the process of autophagy, leads to activation of innate immune response that may be mediated by enhanced toll-like receptor activity. The antigen presenting cells then mediate the differentiation of naïve T-cells into effector T helper (Th) cells, including Th1, Th2, and Th17, which alter gut homeostasis and lead to IBD. In this review, the effects of these components in the immunopathogenesis of IBD will be discussed.
文摘AIM: To report 3 of 120 patients on the German MALT lymphoma trial with H. pylori associated gastric MALT lymphoma who developed early gastric cancer 4 and 5 years, after complete lymphoma remission following cure of H. pylori infection. PATIENTS AND RESULTS: Three patients (two men, 74 and 70 years; one women, 77 years) with H. pylori-associated low-grade MALT lymphoma achieved complete lymphoma remission after being cured. Surveillance endoscopies were performed twice a year in accordance to the protocol. Four years after complete lymphoma remission in two patients, and after 5 years in the other, early gastric adenocarcinoma of the mucosa-type, type IIa and type IIc, respectively, was detected, which were completely removed by endoscopic mucosa resection. In one patient, the gastric cancer was diagnosed at the same location as the previous MALT lymphoma, in the other patients it was detected at different sites of the stomach distant from location of the previous MALT lymphoma. The patients were H. pylori negative during the whole follow-up time. CONCLUSION: These findings strengthen the importance of regular Long-term follow-up endoscopies in patients with complete remission of gastric MALT lymphoma after cure of H. pylori infection. Furthermore, gastric adenocarcinoma may develop despite eradication of H. pylori.
文摘Background Pulmonary mucosa-associated lymphoid tissue （MALT） lymphoma is the most frequent type of non-Hodgkin＇s lymphoma （NHL） that primarily involves the lungs. It represents a rare entity accounting for less than 1% of all NHLs and the clinical features have yet to be clearly elucidated.
文摘Innate sensing of pathogens by pattern-recognition receptors （PRRs） plays essential roles in the innate discrimination between self and non-self components, leading to the generation of innate immune defense and inflammatory responses. The initiation, activation and resolution of innate inflammatory response are mediated by a complex network of interactions among the numerous cellular and molecular components of immune and non- immune system. While a controlled and beneficial innate inflammatory response is critical for the elimination of pathogens and maintenance of tissue homeostasis, dysregulated or sustained inflammation leads to pathological conditions such as chronic infection, inflammatory autoimmune diseases. In this review, we discuss some of the recent advances in our understanding of the cellular and molecular mechanisms for the establishment and reJzulation of innate immunity and inflammatory responses.
文摘The stomach is the most frequently involved site for extranodal lymphomas,accounting for nearly two-thirds of all gastrointestinal cases.It is widely accepted that gastric B-cell,low-grade mucosal-associated lymphoid tissue(MALT)-lymphoma is caused by Helicobacter pylori(H.pylori)infection.MALT-lymphomas may engender different clinical and endoscopic patterns.Often,diagnosis is confirmed in patients with only vague dyspeptic symptoms and without macroscopic lesions on gastric mucosa.H.pylori eradication leads to lymphoma remission in a large number of patients when treatment occurs at an early stage(Ⅰ-Ⅱ1).Neoplasia confined to the submucosa,localized in the antral region of the stomach,and without API2-MALT1 translocation,shows a high probability of remission following H.pylori eradication.When both bacterial infection and lymphoma recur,further eradication therapy is generally effective.Radiotherapy,chemotherapy and,in selected cases,surgery are the available therapeutic options with a high success rate for those patients who fail to achieve remission,while data on immunotherapy with monoclonal antibodies (rituximab)are still scarce.The 5-year survival rate is higher than 90%,but careful,long-term follow-up is required in these patients since lymphoma recurrence has been reported in some cases.
基金by the Division of Intramural Research of NIAID(US National Institutes of Health).
文摘The type 2 immune response is critical for host defense against large parasites such as helminths.On the other hand,dysregulation of the type 2 immune response may cause immunopathological conditions,including asthma,atopic dermatitis,rhinitis,and anaphylaxis.Thus,a balanced type 2 immune response must be achieved to mount effective protection against invading pathogens while avoiding immunopathology.The classical model of type 2 immunity mainly involves the differentiation of type 2 T helper(Th2)cells and the production of distinct type 2 cytokines,including interleukin-4(IL-4),IL-5,and IL-13.Group 2 innate lymphoid cells(ILC2s)were recently recognized as another important source of type 2 cytokines.Although eosinophils,mast cells,and basophils can also express type 2 cytokines and participate in type 2 immune responses to various degrees,the production of type 2 cytokines by the lymphoid lineages,Th2 cells,and ILC2s in particular is the central event during the type 2 immune response.In this review,we discuss recent advances in our understanding of how ILC2s and Th2 cells orchestrate type 2 immune responses through direct and indirect interactions.
基金supported,in part,by the NIH(R01AI121302,R21AI14889801,R01AI074745,and R01AI080769)Kenneth and Judy Betz Professorship at the Mary H.Weiser Food Allergy Center at the University of Michigan to C.H.K.
文摘A mounting body of evidence indicates that dietary fiber(DF)metabolites produced by commensal bacteria play essential roles in balancing the immune system.DF,considered nonessential nutrients in the past,is now considered to be necessary to maintain adequate levels of immunity and suppress inflammatory and allergic responses.Short-chain fatty acids(SCFAs),such as acetate,propionate,and butyrate,are the major DF metabolites and mostly produced by specialized commensal bacteria that are capable of breaking down DF into simpler saccharides and further metabolizing the saccharides into SCFAs.SCFAs act on many cell types to regulate a number of important biological processes,including host metabolism,intestinal functions,and immunity system.This review specifically highlights the regulatory functions of DF and SCFAs in the immune system with a focus on major innate and adaptive lymphocytes.Current information regarding how SCFAs regulate innate lymphoid cells,T helper cells,cytotoxic T cells,and B cells and how these functions impact immunity,inflammation,and allergic responses are discussed.
基金two grants(No.2006AA02Z480 and No.2007AA021109)from the National High Technology Research and Development Program(863 Program)one grant(No.30972776)from the National Natural Science Foundation of China.
文摘Cell-based immunotherapy for lymphoid malignancies has gained increasing attention as patients develop resistance to conventional treatments.cd T cells,which have major histocompatibility complex(MHC)-unrestricted lytic activity,have become a promising candidate population for adoptive cell transfer therapy.We previously established a stable condition for expanding cd T cells by using anti-cd T-cell receptor(TCR)antibody.In this study,we found that adoptive transfer of the expanded cd T cells to Daudi lymphoma-bearing nude mice significantly prolonged the survival time of the mice and improved their living status.We further investigated the characteristics of these antibody-expanded cd T cells compared to the more commonly used phosphoantigen-expanded cd T cells and evaluated the feasibility of employing them in the treatment of lymphoid malignancies.Slow but sustained proliferation of human peripheral blood cd T cells was observed upon stimulation with anti-cd TCR antibody.Compared to phosphoantigen-stimulated cd T cells,the antibody-expanded cells manifested similar functional phenotypes and cytotoxic activity towards lymphoma cell lines.It is noteworthy that the anti-cd TCR antibody could expand both the Vd1 and Vd2 subsets of cd T cells.The in vitro-expanded Vd1 T cells displayed comparable tumour cell-killing activity to Vd2 T cells.Importantly,owing to higher C–C chemokine receptor 4(CCR4)and CCR8 expression,the Vd1 T cells were more prone to infiltrate CCL17-or CCL22-expressing lymphomas than the Vd2 T cells.Characterizing the peripheral blood cd T cells from lymphoma patients further confirmed that the anti-cd TCR antibody-expanded cd T cells could be a more efficacious choice for the treatment of lymphoid malignancies than phosphoantigen-expanded cd T cells.
基金The present work was supported by the National Nature Science Foundation of China(No.81972221,81730102,81920108026,81871964,and 81902422)Emerging Cutting-Edge Technology Joint Research projects of Shanghai(SHDC12017112)+8 种基金the National Ten Thousand Plan Young Top Talents(for Dr.Yanlei Ma)the Shanghai Young Top Talents(for Dr.Yanlei Ma.No.QNBJ1701)the Shanghai Science and Technology Development Fund(No.19410713300,No.20XD1421200)the CSCO-Roche Tumor Research Fund(No.Y-2019Roche-079)the Fudan University Excellence 2025 Talent Cultivation Plan(for Dr.Yanlei Ma)Tongji University Subject Pilot Program(1501141201)Special Construction of Integrated Traditional Chinese Medicine and Western Medicine in Shanghai General Hospital(ZHYY-ZXYJHZX-1-201704)Program of Jiangsu Commission of Health(No.M2020024)Social Development Program of Yangzhou Science and Technology Bureau(No.YZ2020078).
文摘Accumulating evidence suggests that ketogenic diets(KDs)mediate the rise of circulating ketone bodies and exert a potential antiinflammatory effect;however,the consequences of this unique diet on colitis remain unknown.We performed a series of systematic studies using a dextran sulfate sodium(DSS)animal model of inflammatory colitis.Animals were fed with a KD,low-carbohydrate diet(LCD),or normal diet(ND).Germ-free mice were utilized in validation experiments.Colon tissues were analyzed by transcriptome sequencing,RT2 profiler PCR array,histopathology,and immunofluorescence.Serum samples were analyzed by metabolic assay kit.Fecal samples were analyzed by 16S rRNA gene sequencing,liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry.We observed that KD alleviated colitis by altering the gut microbiota and metabolites in a manner distinct from LCD.Quantitative diet experiments confirmed the unique impact of KD relative to LCD with a reproducible increase in Akkermansia,whereas the opposite was observed for Escherichia/Shigella.After colitis induction,the KD protected intestinal barrier function,and reduced the production of R0Ryt+CD3_group 3 innate lymphoid cells(ILC3s)and related inflammatory cytokines(IL-17a,IL-18,IL-22,Ccl4).Finally,fecal microbiota transplantation into germ-free mice revealed that the KD-mediated colitis inhibition and ILC3 regulation were dependent on the modification of gut microbiota.Taken together,our study presents a global view of microbiome-metabolomics changes that occur during KD colitis treatment,and identifies the regulation of gut microbiome and ILC3s as novel targets involving in IBD dietary therapy.
文摘AIM: To investigate treatment outcome of Helicobacter pylori (H.pylori )-negative low-grade gastric mucosaassociated lymphoid tissue (MALT) lymphoma.METHODS: In this study,we retrospectively reviewed the clinical outcome and clinicopathologic factors of stage Ⅰ E H.pylori -negative low-grade gastric MALT lymphoma cases from August 1998 to June 2009.RESULTS: A total of eleven patients with H.pylori -negative low-grade gastric MALT lymphoma were enrolled in the study and received anti-H.pylori eradication treatment and/or radiotherapy or excisional therapy.Complete remission (CR) of gastric MALT lymphoma was achieved in all patients.The time to CR was 1-66 mo (median,1 mo).CONCLUSION: Eradication therapy may be offered as an initial treatment option even in cases of localized H.pylori -negative gastric MALT lymphoma.
文摘Natural killer(NK)cells are innate lymphoid cells endowed with cytolytic activity and a capacity to secrete cytokines and chemokines.Several lines of evidence suggest that NK cells play an important role in anti-tumor immunity.Some therapies against hematological malignacies make use of the immune properties of NK cells,such as their ability to kill residual leukemic blasts efficiently after conditioning during haploidentical hematopoietic stem cell transplantation.However,knowledge on NK cell infiltration and the status of NK cell responsiveness in solid tumors is limited so far.The pro-angiogenic role of the recently described NK cell-like type 1 innate lymphoid cells(ILC1s)and their phenotypic resemblance to NK cells are confounding factors that add a level of complexity,at least in mice.Here,we review the current knowledge on the presence and function of NK cells in solid tumors as well as the immunotherapeutic approaches designed to harness NK cell functions in these conditions,including those that aim to reinforce conventional anti-tumor therapies to increase the chances of successful treatment.
基金supported by CJ Field’s funding from the Natural Sciences and Engineering Council of Canada (NSERC)
文摘The intestine and the gut-associated lymphoid tissue（GALT） are essential components of whole body immune defense,protecting the body from foreign antigens and pathogens,while allowing tolerance to commensal bacteria and dietary antigens.The requirement for protein to support the immune system is well established.Less is known regarding the immune modifying properties of individual amino acids,particularly on the GALT.Both oral and parenteral feeding studies have established convincing evidence that not only the total protein intake,but the availability of specific dietary amino acids（in particular glutamine,glutamate,and arginine,and perhaps methionine,cysteine and threonine） are essential to optimizing the immune functions of the intestine and the proximal resident immune cells.These amino acids each have unique properties that include,maintaining the integrity,growth and function of the intestine,as well as normalizing inflammatory cytokine secretion and improving T-lymphocyte numbers,specific T cell functions,and the secretion of IgA by lamina propria cells.Our understanding of this area has come from studies that have supplemented single amino acids to a mixed protein diet and measuring the effect on specific immune parameters.Future studies should be designed using amino acid mixtures that target a number of specific functions of GALT in order to optimize immune function in domestic animals and humans during critical periods of development and various disease states.
文摘Gastrointestinal lymphoma is the most common type of extranodal lymphoma,and most commonly affects the stomach.Marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue(MALT)and diffuse large B-cell lymphoma are the most common histologic types of gastric lymphoma.Despite its increasing incidence,diagnosis of gastric lymphoma is difficult at an earlier stage due to its nonspecific symptoms and endoscopic findings,and,thus,a high index of suspicion,and multiple,deep,repeated biopsies at abnormally and normally appearing sites in the stomach are needed.In addition,testing for Helicobacter pylori(H.pylori)infection and endoscopic ultrasonography to determine the depth of tumor invasion and involvement of regional lymph nodes is essential for predicting response to H.pylori eradication and for assessment of disease progression.In addition,H.pylori infection and MALT lymphoma development are associated,and complete regression of low-grade MALT lymphomas after H.pylori eradication has been demonstrated.Radiotherapy and/or chemotherapy can be used in cases that show poor response to H.pylori eradication,negativity for H.pylori infection,or high-grade lymphoma.
基金This work was supported by the National Natural Science Foundations of China(Nos.81972532,81772896,81602383 and 81472524)the Science and Technology Planning Project of Guangzhou City of China(No.2017004020102).
文摘Tertiary lymphoid structures(TLS)are ectopic lymphoid structures in cancers that are largely associated with favourable prognosis.However,the prognostic value of TLSs in oral squamous cell carcinoma(OSCC)is largely unknown,and the association between tumour infiltrating lymphocytes(TILs)and TLSs has been rarely explored in OSCC.In this study,associated markers of TLS,including peripheral node address(PNAd)in high endothelial venules,CD20 in B cells and CD3 in T cells,were examined in 168 OSCC patients,and survival analysis was performed between TLS-positive and TLS-negative cohorts.We detected the presence of TILs by staining CD8+cytotoxic T cells and CD57+NK cells as well.TLSs appeared as highly organized structures in 45(26.8%)cases.TLSpositive patients had a better 5-year overall survival(OS)rate(88.9%vs.56.1%,P<0.001)and relapse-free survival(RFS)rate(88.9%vs.63.4%,P=0.002).Moreover,the presence of TLS was an independent prognostic factor for both the 5-year OS rate(hazard ratio[HR]=3.784;95%confidence interval[CI],1.498–9.562)and RFS rate(HR=3.296;95%CI,1.279–8.490)in multivariate analysis.Furthermore,a higher density of CD8+T cells and CD57+NK cells was found in TLS-positive sections than in TLS-negative counterparts(P<0.001),and their combination provided a higher predictive accuracy(AUC=0.730;95%CI,0.654–0.805).In conclusion,our results suggest that TLS is an independent positive prognostic factor for OSCC patients.These findings provide a theoretical basis for the future diagnostic and therapeutic value of TLSs in OSCC treatment.
