There exist differences in the epidemiological characteristics,clinicopathological features,tumor biological characteristics,treatment patterns,and drug selections between gastric cancer patients from the Eastern and ...There exist differences in the epidemiological characteristics,clinicopathological features,tumor biological characteristics,treatment patterns,and drug selections between gastric cancer patients from the Eastern and Western countries.The Chinese Society of Clinical Oncology(CSCO)has organized a panel of senior experts specializing in all sub-specialties of gastric cancer to compile a clinical guideline for the diagnosis and treatment of gastric cancer since 2016 and renews it annually.Taking into account regional differences,giving full consideration to the accessibility of diagnosis and treatment resources,these experts have conducted expert consensus judgment on relevant evidence and made various grades of recommendations for the clinical diagnosis and treatment of gastric cancer to reflect the value of cancer treatment and meeting health economic indexes in China.The 2021 CSCO Clinical Practice Guidelines for Gastric Cancer covers the diagnosis,treatment,follow-up,and screening of gastric cancer.Based on the 2020 version of the CSCO Chinese Gastric Cancer guidelines,this updated guideline integrates the results ofmajor clinical studies from China and overseas for the past year,focused on the inclusion of research data from the Chinese population for more personalized and clinically relevant recommendations.For the comprehensive treatment of non-metastatic gastric cancer,attentions were paid to neoadjuvant treatment.The value of perioperative chemotherapy is gradually becoming clearer and its recommendation level has been updated.For the comprehensive treatment of metastatic gastric cancer,recommendations for immunotherapy were included,and immune checkpoint inhibitors fromthird-line to the first-line of treatment for different patient groups with detailed notes are provided.展开更多
China is one of the countries with the highest incidence of gastric cancer.There are differences in epidemiological characteristics,clinicopathological features,tumor biological characteristics,treatment patterns,and ...China is one of the countries with the highest incidence of gastric cancer.There are differences in epidemiological characteristics,clinicopathological features,tumor biological characteristics,treatment patterns,and drug selection between gastric cancer patients from the Eastern and Western countries.Non-Chinese guidelines cannot specifically reflect the diagnosis and treatment characteristics for the Chinese gastric cancer patients.The Chinese Society of Clinical Oncology(CSCO)arranged for a panel of senior experts specializing in all sub-specialties of gastric cancer to compile,discuss,and revise the guidelines on the diagnosis and treatment of gastric cancer based on the findings of evidence-based medicine in China and abroad.By referring to the opinions of industry experts,taking into account of regional differences,giving full consideration to the accessibility of diagnosis and treatment resources,these experts have conducted experts’consensus judgement on relevant evidence and made various grades of recommendations for the clinical diagnosis and treatment of gastric cancer to reflect the value of cancer treatment and meeting health economic indexes.This guideline uses tables and is complemented by explanatory and descriptive notes covering the diagnosis,comprehensive treatment,and follow-up visits for gastric cancer.展开更多
<Abstract>Background and Objective:Cytokine-induced killer(CIK) cells and autologous dendritic cells-CIK(DCCIK) cells co-cultured with autologous dendritic cells(DCs) and CIK cells are commonly used for immunoth...<Abstract>Background and Objective:Cytokine-induced killer(CIK) cells and autologous dendritic cells-CIK(DCCIK) cells co-cultured with autologous dendritic cells(DCs) and CIK cells are commonly used for immunotherapy recently.We compared the anti-tumor immune response of CIK cells,autologous DC-CIK cells,and semi-allogeneic DC-CIK cells to explore a more effective anti-tumor adoptive immunotherapy approach.Met hods:Peripheral monocytes were isolated from patients with renal carcinoma,lung cancer,or maxillary squamous cell carcinoma and their healthy adult children.Isolated cells were cultured and induced as DCs and CIK cells in vitro.CIK cells from patients were co-cultured with autologous DCs and DCs from their children respectively,generating DC-CIK cells and semi-allogeneic DC-CIK cells.The anti-tumor activities of autologous CIK cells,autologous DC-CIK cells,and semi-allogeneic DC-CIK cells were measured by LDH assay.Intracellular staining was used to test the secretion of cytokines.Flow cytometry was applied for detecting the phonotype changes of these three types of cells.Cell proliferation and cell apoptosis were detected by 5,6carboxyfluorescein diacetate succinimidyl ester(CFSE) and Annexin V/PI respectively.Result s:Compared with autologous CIK cells and DC-CIK cells,semi-allogeneic DC-CIK cells significantly enhanced the anti-tumor activity and IFN-γ secretion,reduced IL-4 secretion,increased the ratio of CD3+CD56+ cells and CD3+CD8+ cells,decreased the number of CD4+CD25+ cells,promoted cell proliferation,and lessened cell apoptosis.Conclusions:Semi-allogeneic DC-CIK cells had a stronger anti-tumor effect than did autologous CIK cells and DC-CIK cells.Our results provided experimental evidence for clinical application of DC-CIK cells.展开更多
AIM: To characterize the anticancer function of cytokine-induced killer cells (CIK) and develop an adoptive immunotherapy for the patients with primary hepatocellular carcinoma (HCC), we evaluated the proliferation ra...AIM: To characterize the anticancer function of cytokine-induced killer cells (CIK) and develop an adoptive immunotherapy for the patients with primary hepatocellular carcinoma (HCC), we evaluated the proliferation rate, phenotype and the antitumor activity of human CIK cells from healthy donors and HCC patients in vitro and in vivo. METHODS: Peripheral blood mononuclear cells (PBMC) from healthy donors and patients with primary HCC were incubated in vitro and induced into CIK cells in the presence of various cytokines such as interferon-gamma (IFN-gamma), interleukin-1 (IL-1), IL-2 and monoclonal antibody (mAb) against CD3. The phenotype and characterization of CIK cells were identified by flow cytometric analysis. The cytotoxicity of CIK cells was determined by (51)Cr release assay. RESULTS: The CIK cells were shown to be a heterogeneous population with different cellular phenotypes. The percentage of CD3+/CD56+ positive cells, the dominant effector cells, in total CIK cells from healthy donors and HCC patients, significantly increased from 0.1-0.13% at day 0 to 19.0-20.5% at day 21 incubation, which suggested that the CD3+ CD56+ positive cells proliferated faster than other cell populations of CIK cells in the protocol used in this study. After 28 day in vitro incubation, the CIK cells from patients with HCC and healthy donors increased by more than 300-fold and 500-fold in proliferation cell number, respectively. CIK cells originated from HCC patients possessed a higher in vitro antitumor cytotoxic activity on autologous HCC cells than the autologous lymphokine-activated killer (LAK) cells and PBMC cells. In in vivo animal experiment, CIK cells had stronger effects on the inhibition of tumor growth in Balb/c nude mice bearing BEL-7402-producing tumor than LAK cells (mean inhibitory rate, 84.7% vs 52.8%, P【0.05) or PBMC (mean inhibitory rate, 84.7% vs 37.1%, P【0.01). CONCLUSION: Autologous CIK cells are of highly efficient cytotoxic effector cells against primary hepatocellular carcinoma cells and might 展开更多
In China,lung cancer is a primary cancer type with high incidence and mortality.Risk factors for lung cancer include tobacco use,family history,radiation exposure,and the presence of chronic lung diseases.Most early-...In China,lung cancer is a primary cancer type with high incidence and mortality.Risk factors for lung cancer include tobacco use,family history,radiation exposure,and the presence of chronic lung diseases.Most early-stage non-small cell lung cancer(NSCLC)patients miss the optimal timing for treatment due to the lack of clinical presentations.Population-based nationwide screening programs are of significant help in increasing the early detection and survival rates of NSCLC in China.The understanding of molecular carcinogenesis and the identification of oncogenic drivers dramatically facilitate the development of targeted therapy for NSCLC,thus prolonging survival in patients with positive drivers.In the exploration of immune escape mechanisms,programmed cell death protein 1(PD-1)/programmed death-ligand 1(PD-L1)inhibitor monotherapy and PD-1/PD-L1 inhibitor plus chemotherapy have become a standard of care for advanced NSCLC in China.In the Chinese Society of Clinical Oncology’s guidelines for NSCLC,maintenance immunotherapy is recommended for locally advanced NSCLC after chemoradiotherapy.Adjuvant immunotherapy and neoadjuvant chemoimmunotherapy will be approved for resectable NSCLC.In this review,we summarized recent advances in NSCLC in China in terms of epidemiology,biology,molecular pathology,pathogenesis,screening,diagnosis,targeted therapy,and immunotherapy。展开更多
目的评估联合抗炎和免疫刺激治疗严重脓毒症方法的有效性。方法本研究采用多中心、前瞻、随机、对照方法。共433例患者进入本研究。进入 ICU 内严重脓毒症(Marshall 评分5～20)的患者入选,随机分为对照组:常规治疗;治疗组1(第1阶段):常...目的评估联合抗炎和免疫刺激治疗严重脓毒症方法的有效性。方法本研究采用多中心、前瞻、随机、对照方法。共433例患者进入本研究。进入 ICU 内严重脓毒症(Marshall 评分5～20)的患者入选,随机分为对照组:常规治疗;治疗组1(第1阶段):常规治疗+乌司他丁30万 U/日,α1胸腺肽(迈普新)1.6 mg/d,连续7 d;治疗组2(第2阶段):常规治疗+乌司他丁60万 U/日,迈普新3.2 mg/日,连续7 d,进行28 d 和90 d 预后等疗效评估。结果第1阶段91例,治疗组(治疗组1)与对照组28 d 预后等各项疗效评估指标差异均无统计学意义。第2阶段342例,治疗组(治疗组2)与对照组相比(意向治疗分析),28 d 病死率为25.1%vs 38.3%(P=0.0088),90 d 病死率为37.1%vs 52.1%(P=0.0054),28 d APACHEⅡ评分12.7±9.4 vs 14.3±9.2(P=0.0384),28 d 单核细胞 HLA-DR/CD14+(51.7±26.5)%vs(40.1±22.0)%(P=0.0092)。其他疗效评估指标,如 ICU内治疗天数、呼吸机使用天数、抗生素使用时间等,两组差异无统计学意义。结论本研究治疗方案能够明显改善严重脓毒症患者28 d 和90 d 预后,具有积极推广价值;治疗的有效性具有剂量依赖性,最佳剂量有待进一步探讨。展开更多
Immunotherapy has revolutionized cancer treatment and rejuvenated the field of tumor immunology.Several types of immunotherapy,including adoptive cell transfer(ACT)and immune checkpoint inhibitors(ICIs),have obtained ...Immunotherapy has revolutionized cancer treatment and rejuvenated the field of tumor immunology.Several types of immunotherapy,including adoptive cell transfer(ACT)and immune checkpoint inhibitors(ICIs),have obtained durable clinical responses,but their efficacies vary,and only subsets of cancer patients can benefit from them.Immune infiltrates in the tumor microenvironment(TME)have been shown to play a key role in tumor development and will affect the clinical outcomes of cancer patients.Comprehensive profiling of tumor-infiltrating immune cells would shed light on the mechanisms of cancer–immune evasion,thus providing opportunities for the development of novel therapeutic strategies.However,the highly heterogeneous and dynamic nature of the TME impedes the precise dissection of intratumoral immune cells.With recent advances in single-cell technologies such as single-cell RNA sequencing(scRNA-seq)and mass cytometry,systematic interrogation of the TME is feasible and will provide insights into the functional diversities of tumor-infiltrating immune cells.In this review,we outline the recent progress in cancer immunotherapy,particularly by focusing on landmark studies and the recent single-cell characterization of tumor-associated immune cells,and we summarize the phenotypic diversities of intratumoral immune cells and their connections with cancer immunotherapy.We believe such a review could strengthen our understanding of the progress in cancer immunotherapy,facilitate the elucidation of immune cell modulation in tumor progression,and thus guide the development of novel immunotherapies for cancer treatment.展开更多
AIM: To analyze the correlation between cytokineinduced killer (CIK) cells adoptive immunotherapy and cancer-related death in gastric cancer patients. METHODS: One hundred and fifty-six gastric cancer patients after o...AIM: To analyze the correlation between cytokineinduced killer (CIK) cells adoptive immunotherapy and cancer-related death in gastric cancer patients. METHODS: One hundred and fifty-six gastric cancer patients after operation at the Third Affiliated Hospital of Soochow University were enrolled in this study. Their clinical data including demographic characteristics, operation time, tumor size, pathological type and staging, tumor metastasis, outcome of chemotherapy or CIK cells adoptive immunotherapy, survival time or time of death were collected with a standard structured questionnaire. Kaplan-Meier method was used to estimate the median survival time, and the 2- and 5- year survival rates. Hazard risk (HR) and 95% confidence interval (95% CI) of CIK cells adoptive immunotherapy for gastric cancer were calculated using the two-stage time-dependent covariates Cox model. RESULTS: The survival time of gastric cancer patients was longer after CIK cells adoptive immunotherapy than after chemotherapy (χ 2 = 10.907, P = 0.001). The median survival time of gastric cancer patients was also longer after CIK cells adoptive immunotherapy than after chemotherapy (49 mo vs 27 mo, P < 0.05). The 2- and 5-year survival rates of gastric cancer patients were significantly higher after CIK cells adoptive immunotherapy than after chemotherapy (73.5% vs 52.6%, 40.4% vs 23.9%, P < 0.05). A significant difference was observed in the survival curve for patients who received CIK cells adoptive immunotherapy (0, 1-10, 11-25, and over 25 frequencies) (χ 2 = 14.534, P = 0.002). The frequencies of CIK cells adoptive immunotherapy were significantly related with the decreasing risk of death in gastric cancer patients after adjustment for sex and age of the patients, tumor stage and relapse (HR = 0.54, 95% CI: 0.36-0.80) when the first stage Cox model was used to define the subjects who remained alive beyond 36 mo as survivors. However, no correlation was observed between the frequencies of death in CIK cells adoptive immunotherapy and the 展开更多
Natural killer （NK） cells play critical roles in host immunity against cancer. In response, cancers develop mechanisms to escape NK cell attack or induce defective NK cells. Current NK cell-based cancer immunotherap...Natural killer （NK） cells play critical roles in host immunity against cancer. In response, cancers develop mechanisms to escape NK cell attack or induce defective NK cells. Current NK cell-based cancer immunotherapy aims to overcome NK cell paralysis using several approaches. One approach uses expanded allogeneic NK cells, which are not inhibited by self histocompatibility antigens like autologous NK cells, for adoptive cellular immunotherapy. Another adoptive transfer approach uses stable allogeneic NK cell lines, which is more practical for quality control and large-scale production. A third approach is genetic modification of fresh NK cells or NK cell lines to highly express cytokines, Fc receptors and/or chimeric tumor-antigen receptors. Therapeutic NK cells can be derived from various sources, including peripheral or cord blood cells, stem cells or even induced pluripotent stem cells （iPSCs）, and a variety of stimulators can be used for large-scale production in laboratories or good manufacturing practice （GMP） facilities, including soluble growth factors, immobilized molecules or antibodies, and other cellular activators. A list of NK cell therapies to treat several types of cancer in clinical trials is reviewed here. Several different approaches to NK-based immunotherapy, such as tissue-specific NK cells, killer receptor-oriented NK cells and chemically treated NK cells, are discussed. A few new techniques or strategies to monitor NK cell therapy by non-invasive imaging, predetermine the efficiency of NK cell therapy by in vivo experiments and evaluate NK cell therapy approaches in clinical trials are also introduced.展开更多
文摘There exist differences in the epidemiological characteristics,clinicopathological features,tumor biological characteristics,treatment patterns,and drug selections between gastric cancer patients from the Eastern and Western countries.The Chinese Society of Clinical Oncology(CSCO)has organized a panel of senior experts specializing in all sub-specialties of gastric cancer to compile a clinical guideline for the diagnosis and treatment of gastric cancer since 2016 and renews it annually.Taking into account regional differences,giving full consideration to the accessibility of diagnosis and treatment resources,these experts have conducted expert consensus judgment on relevant evidence and made various grades of recommendations for the clinical diagnosis and treatment of gastric cancer to reflect the value of cancer treatment and meeting health economic indexes in China.The 2021 CSCO Clinical Practice Guidelines for Gastric Cancer covers the diagnosis,treatment,follow-up,and screening of gastric cancer.Based on the 2020 version of the CSCO Chinese Gastric Cancer guidelines,this updated guideline integrates the results ofmajor clinical studies from China and overseas for the past year,focused on the inclusion of research data from the Chinese population for more personalized and clinically relevant recommendations.For the comprehensive treatment of non-metastatic gastric cancer,attentions were paid to neoadjuvant treatment.The value of perioperative chemotherapy is gradually becoming clearer and its recommendation level has been updated.For the comprehensive treatment of metastatic gastric cancer,recommendations for immunotherapy were included,and immune checkpoint inhibitors fromthird-line to the first-line of treatment for different patient groups with detailed notes are provided.
文摘China is one of the countries with the highest incidence of gastric cancer.There are differences in epidemiological characteristics,clinicopathological features,tumor biological characteristics,treatment patterns,and drug selection between gastric cancer patients from the Eastern and Western countries.Non-Chinese guidelines cannot specifically reflect the diagnosis and treatment characteristics for the Chinese gastric cancer patients.The Chinese Society of Clinical Oncology(CSCO)arranged for a panel of senior experts specializing in all sub-specialties of gastric cancer to compile,discuss,and revise the guidelines on the diagnosis and treatment of gastric cancer based on the findings of evidence-based medicine in China and abroad.By referring to the opinions of industry experts,taking into account of regional differences,giving full consideration to the accessibility of diagnosis and treatment resources,these experts have conducted experts’consensus judgement on relevant evidence and made various grades of recommendations for the clinical diagnosis and treatment of gastric cancer to reflect the value of cancer treatment and meeting health economic indexes.This guideline uses tables and is complemented by explanatory and descriptive notes covering the diagnosis,comprehensive treatment,and follow-up visits for gastric cancer.
基金supported by Poten Biomedical Technology Development Co.,Ltd.
文摘<Abstract>Background and Objective:Cytokine-induced killer(CIK) cells and autologous dendritic cells-CIK(DCCIK) cells co-cultured with autologous dendritic cells(DCs) and CIK cells are commonly used for immunotherapy recently.We compared the anti-tumor immune response of CIK cells,autologous DC-CIK cells,and semi-allogeneic DC-CIK cells to explore a more effective anti-tumor adoptive immunotherapy approach.Met hods:Peripheral monocytes were isolated from patients with renal carcinoma,lung cancer,or maxillary squamous cell carcinoma and their healthy adult children.Isolated cells were cultured and induced as DCs and CIK cells in vitro.CIK cells from patients were co-cultured with autologous DCs and DCs from their children respectively,generating DC-CIK cells and semi-allogeneic DC-CIK cells.The anti-tumor activities of autologous CIK cells,autologous DC-CIK cells,and semi-allogeneic DC-CIK cells were measured by LDH assay.Intracellular staining was used to test the secretion of cytokines.Flow cytometry was applied for detecting the phonotype changes of these three types of cells.Cell proliferation and cell apoptosis were detected by 5,6carboxyfluorescein diacetate succinimidyl ester(CFSE) and Annexin V/PI respectively.Result s:Compared with autologous CIK cells and DC-CIK cells,semi-allogeneic DC-CIK cells significantly enhanced the anti-tumor activity and IFN-γ secretion,reduced IL-4 secretion,increased the ratio of CD3+CD56+ cells and CD3+CD8+ cells,decreased the number of CD4+CD25+ cells,promoted cell proliferation,and lessened cell apoptosis.Conclusions:Semi-allogeneic DC-CIK cells had a stronger anti-tumor effect than did autologous CIK cells and DC-CIK cells.Our results provided experimental evidence for clinical application of DC-CIK cells.
基金Science and Technology Development Foundation of Beijing Institute of Infectious Diseases,No.01 Z094
文摘AIM: To characterize the anticancer function of cytokine-induced killer cells (CIK) and develop an adoptive immunotherapy for the patients with primary hepatocellular carcinoma (HCC), we evaluated the proliferation rate, phenotype and the antitumor activity of human CIK cells from healthy donors and HCC patients in vitro and in vivo. METHODS: Peripheral blood mononuclear cells (PBMC) from healthy donors and patients with primary HCC were incubated in vitro and induced into CIK cells in the presence of various cytokines such as interferon-gamma (IFN-gamma), interleukin-1 (IL-1), IL-2 and monoclonal antibody (mAb) against CD3. The phenotype and characterization of CIK cells were identified by flow cytometric analysis. The cytotoxicity of CIK cells was determined by (51)Cr release assay. RESULTS: The CIK cells were shown to be a heterogeneous population with different cellular phenotypes. The percentage of CD3+/CD56+ positive cells, the dominant effector cells, in total CIK cells from healthy donors and HCC patients, significantly increased from 0.1-0.13% at day 0 to 19.0-20.5% at day 21 incubation, which suggested that the CD3+ CD56+ positive cells proliferated faster than other cell populations of CIK cells in the protocol used in this study. After 28 day in vitro incubation, the CIK cells from patients with HCC and healthy donors increased by more than 300-fold and 500-fold in proliferation cell number, respectively. CIK cells originated from HCC patients possessed a higher in vitro antitumor cytotoxic activity on autologous HCC cells than the autologous lymphokine-activated killer (LAK) cells and PBMC cells. In in vivo animal experiment, CIK cells had stronger effects on the inhibition of tumor growth in Balb/c nude mice bearing BEL-7402-producing tumor than LAK cells (mean inhibitory rate, 84.7% vs 52.8%, P【0.05) or PBMC (mean inhibitory rate, 84.7% vs 37.1%, P【0.01). CONCLUSION: Autologous CIK cells are of highly efficient cytotoxic effector cells against primary hepatocellular carcinoma cells and might
基金National Natural Science Foundation of China,Grant/Award Number:81871865Collaborative Innovation Program of Shanghai Municipal Health Commission,Grant/Award Number:2020CXJQ02Science and Technology Innovation Action Plan Project of Shanghai Municipal Science and Technology Commission,Grant/Award Numbers:19411950300,19411950301。
文摘In China,lung cancer is a primary cancer type with high incidence and mortality.Risk factors for lung cancer include tobacco use,family history,radiation exposure,and the presence of chronic lung diseases.Most early-stage non-small cell lung cancer(NSCLC)patients miss the optimal timing for treatment due to the lack of clinical presentations.Population-based nationwide screening programs are of significant help in increasing the early detection and survival rates of NSCLC in China.The understanding of molecular carcinogenesis and the identification of oncogenic drivers dramatically facilitate the development of targeted therapy for NSCLC,thus prolonging survival in patients with positive drivers.In the exploration of immune escape mechanisms,programmed cell death protein 1(PD-1)/programmed death-ligand 1(PD-L1)inhibitor monotherapy and PD-1/PD-L1 inhibitor plus chemotherapy have become a standard of care for advanced NSCLC in China.In the Chinese Society of Clinical Oncology’s guidelines for NSCLC,maintenance immunotherapy is recommended for locally advanced NSCLC after chemoradiotherapy.Adjuvant immunotherapy and neoadjuvant chemoimmunotherapy will be approved for resectable NSCLC.In this review,we summarized recent advances in NSCLC in China in terms of epidemiology,biology,molecular pathology,pathogenesis,screening,diagnosis,targeted therapy,and immunotherapy。
文摘目的评估联合抗炎和免疫刺激治疗严重脓毒症方法的有效性。方法本研究采用多中心、前瞻、随机、对照方法。共433例患者进入本研究。进入 ICU 内严重脓毒症(Marshall 评分5～20)的患者入选,随机分为对照组:常规治疗;治疗组1(第1阶段):常规治疗+乌司他丁30万 U/日,α1胸腺肽(迈普新)1.6 mg/d,连续7 d;治疗组2(第2阶段):常规治疗+乌司他丁60万 U/日,迈普新3.2 mg/日,连续7 d,进行28 d 和90 d 预后等疗效评估。结果第1阶段91例,治疗组(治疗组1)与对照组28 d 预后等各项疗效评估指标差异均无统计学意义。第2阶段342例,治疗组(治疗组2)与对照组相比(意向治疗分析),28 d 病死率为25.1%vs 38.3%(P=0.0088),90 d 病死率为37.1%vs 52.1%(P=0.0054),28 d APACHEⅡ评分12.7±9.4 vs 14.3±9.2(P=0.0384),28 d 单核细胞 HLA-DR/CD14+(51.7±26.5)%vs(40.1±22.0)%(P=0.0092)。其他疗效评估指标,如 ICU内治疗天数、呼吸机使用天数、抗生素使用时间等,两组差异无统计学意义。结论本研究治疗方案能够明显改善严重脓毒症患者28 d 和90 d 预后,具有积极推广价值;治疗的有效性具有剂量依赖性,最佳剂量有待进一步探讨。
基金This work was supported by grants from the Beijing Advanced Innovation Center for Genomics at Peking University,Key Technologies R&D Program(2016YFC0900100 and 2016YFC0902300)the National Natural Science Foundation of China(31530036 and 91742203).
文摘Immunotherapy has revolutionized cancer treatment and rejuvenated the field of tumor immunology.Several types of immunotherapy,including adoptive cell transfer(ACT)and immune checkpoint inhibitors(ICIs),have obtained durable clinical responses,but their efficacies vary,and only subsets of cancer patients can benefit from them.Immune infiltrates in the tumor microenvironment(TME)have been shown to play a key role in tumor development and will affect the clinical outcomes of cancer patients.Comprehensive profiling of tumor-infiltrating immune cells would shed light on the mechanisms of cancer–immune evasion,thus providing opportunities for the development of novel therapeutic strategies.However,the highly heterogeneous and dynamic nature of the TME impedes the precise dissection of intratumoral immune cells.With recent advances in single-cell technologies such as single-cell RNA sequencing(scRNA-seq)and mass cytometry,systematic interrogation of the TME is feasible and will provide insights into the functional diversities of tumor-infiltrating immune cells.In this review,we outline the recent progress in cancer immunotherapy,particularly by focusing on landmark studies and the recent single-cell characterization of tumor-associated immune cells,and we summarize the phenotypic diversities of intratumoral immune cells and their connections with cancer immunotherapy.We believe such a review could strengthen our understanding of the progress in cancer immunotherapy,facilitate the elucidation of immune cell modulation in tumor progression,and thus guide the development of novel immunotherapies for cancer treatment.
基金Supported by The National Natural Science Foundation of China, No. 30872176, 30950022 and 30972703grants of Jiangsu Province and Soochow University Medical Development Foundation, No. EE126765
文摘AIM: To analyze the correlation between cytokineinduced killer (CIK) cells adoptive immunotherapy and cancer-related death in gastric cancer patients. METHODS: One hundred and fifty-six gastric cancer patients after operation at the Third Affiliated Hospital of Soochow University were enrolled in this study. Their clinical data including demographic characteristics, operation time, tumor size, pathological type and staging, tumor metastasis, outcome of chemotherapy or CIK cells adoptive immunotherapy, survival time or time of death were collected with a standard structured questionnaire. Kaplan-Meier method was used to estimate the median survival time, and the 2- and 5- year survival rates. Hazard risk (HR) and 95% confidence interval (95% CI) of CIK cells adoptive immunotherapy for gastric cancer were calculated using the two-stage time-dependent covariates Cox model. RESULTS: The survival time of gastric cancer patients was longer after CIK cells adoptive immunotherapy than after chemotherapy (χ 2 = 10.907, P = 0.001). The median survival time of gastric cancer patients was also longer after CIK cells adoptive immunotherapy than after chemotherapy (49 mo vs 27 mo, P < 0.05). The 2- and 5-year survival rates of gastric cancer patients were significantly higher after CIK cells adoptive immunotherapy than after chemotherapy (73.5% vs 52.6%, 40.4% vs 23.9%, P < 0.05). A significant difference was observed in the survival curve for patients who received CIK cells adoptive immunotherapy (0, 1-10, 11-25, and over 25 frequencies) (χ 2 = 14.534, P = 0.002). The frequencies of CIK cells adoptive immunotherapy were significantly related with the decreasing risk of death in gastric cancer patients after adjustment for sex and age of the patients, tumor stage and relapse (HR = 0.54, 95% CI: 0.36-0.80) when the first stage Cox model was used to define the subjects who remained alive beyond 36 mo as survivors. However, no correlation was observed between the frequencies of death in CIK cells adoptive immunotherapy and the
文摘Natural killer （NK） cells play critical roles in host immunity against cancer. In response, cancers develop mechanisms to escape NK cell attack or induce defective NK cells. Current NK cell-based cancer immunotherapy aims to overcome NK cell paralysis using several approaches. One approach uses expanded allogeneic NK cells, which are not inhibited by self histocompatibility antigens like autologous NK cells, for adoptive cellular immunotherapy. Another adoptive transfer approach uses stable allogeneic NK cell lines, which is more practical for quality control and large-scale production. A third approach is genetic modification of fresh NK cells or NK cell lines to highly express cytokines, Fc receptors and/or chimeric tumor-antigen receptors. Therapeutic NK cells can be derived from various sources, including peripheral or cord blood cells, stem cells or even induced pluripotent stem cells （iPSCs）, and a variety of stimulators can be used for large-scale production in laboratories or good manufacturing practice （GMP） facilities, including soluble growth factors, immobilized molecules or antibodies, and other cellular activators. A list of NK cell therapies to treat several types of cancer in clinical trials is reviewed here. Several different approaches to NK-based immunotherapy, such as tissue-specific NK cells, killer receptor-oriented NK cells and chemically treated NK cells, are discussed. A few new techniques or strategies to monitor NK cell therapy by non-invasive imaging, predetermine the efficiency of NK cell therapy by in vivo experiments and evaluate NK cell therapy approaches in clinical trials are also introduced.
