In patients with inflammatory bowel disease(IBD), chronic inflammation is a major risk factor for the development of gastrointestinal malignancies. The pathogenesis of colitis-associated cancer is distinct from sporad...In patients with inflammatory bowel disease(IBD), chronic inflammation is a major risk factor for the development of gastrointestinal malignancies. The pathogenesis of colitis-associated cancer is distinct from sporadic colorectal carcinoma and the critical molecular mechanisms underlying this process have yet to be elucidated. Patients with IBD have also been shown to be at increased risk of developing extra-intestinal malignancies. Medical therapies that diminish the mucosal inflammatory response represent the foundation of treatment in IBD, and recent evidence supports their introduction earlier in the disease course. However, therapies that alter the immune system, often used for long durations, may also promote carcinogenesis. As the population of patients with IBD grows older, with longer duration of chronic inflammation and longer exposure to immunosuppression, there is an increasing risk of cancer development. Many of these patients will require cancer treatment, including chemotherapy, radiation, hormonal therapy, and surgery. Many patients will require further treatment for their IBD. This review seeks to explore the characteristics and risks of cancer in patients with IBD, and to evaluate the limited data on patients with IBD and cancer, including management of IBD after a diagnosis of cancer, the effects of cancer treatment on IBD, and the effect of IBD and medications for IBD on cancer outcomes.展开更多
Emerging evidence suggests that the clinical success of conventional chemotherapy is not solely attributed to tumor cell toxicity,but also results from the restoration of immunosurveillance,which has been largely negl...Emerging evidence suggests that the clinical success of conventional chemotherapy is not solely attributed to tumor cell toxicity,but also results from the restoration of immunosurveillance,which has been largely neglected in the past preclinical and clinical research.Antitumor immune response can be primed by immunogenic cell death(ICD),a type of cell death characterized by cell-surface translocation of calreticulin(CRT),extracellular release of ATP and high mobility group box 1(HMGB1),and stimulation of type I interferon(IFN)responses.Here we summarize recent studies showing conventional chemotherapeutics as ICD inducers,which are capable of modulating tumor infiltrating lymphocytes(TILs)and reactivating antitumor immunity within an immuno-suppressive microenvironment.Such immunological effects of conventional chemotherapy are likely critical for better prognosis of cancer patients.Furthermore,combination of ICD-inducing chemotherapeutics with immunotherapy is a promising approach for improving the clinical outcomes of cancer patients.展开更多
Epigenomic imbalance drives abnormal transcriptional processes,promoting the onset and progression of cancer.Although defective gene regulation generally affects carcinogenesis and tumor suppression networks,tumor imm...Epigenomic imbalance drives abnormal transcriptional processes,promoting the onset and progression of cancer.Although defective gene regulation generally affects carcinogenesis and tumor suppression networks,tumor immunogenicity and immune cells involved in antitumor responses may also be affected by epigenomic changes,which may have significant implications for the development and application of epigenetic therapy,cancer immunotherapy,and their combinations.Herein,we focus on the impact of epigenetic regulation on tumor immune cell function and the role of key abnormal epigenetic processes,DNA methylation,histone post-translational modification,and chromatin structure in tumor immunogenicity,and introduce these epigenetic research methods.We emphasize the value of small-molecule inhibitors of epigenetic modulators in enhancing antitumor immune responses and discuss the challenges of developing treatment plans that combine epigenetic therapy and immuno-therapy through the complex interaction between cancer epigenetics and cancer immunology.展开更多
文摘In patients with inflammatory bowel disease(IBD), chronic inflammation is a major risk factor for the development of gastrointestinal malignancies. The pathogenesis of colitis-associated cancer is distinct from sporadic colorectal carcinoma and the critical molecular mechanisms underlying this process have yet to be elucidated. Patients with IBD have also been shown to be at increased risk of developing extra-intestinal malignancies. Medical therapies that diminish the mucosal inflammatory response represent the foundation of treatment in IBD, and recent evidence supports their introduction earlier in the disease course. However, therapies that alter the immune system, often used for long durations, may also promote carcinogenesis. As the population of patients with IBD grows older, with longer duration of chronic inflammation and longer exposure to immunosuppression, there is an increasing risk of cancer development. Many of these patients will require cancer treatment, including chemotherapy, radiation, hormonal therapy, and surgery. Many patients will require further treatment for their IBD. This review seeks to explore the characteristics and risks of cancer in patients with IBD, and to evaluate the limited data on patients with IBD and cancer, including management of IBD after a diagnosis of cancer, the effects of cancer treatment on IBD, and the effect of IBD and medications for IBD on cancer outcomes.
基金supported U.S.National Institutes of Health grants(R01CA172136,R01CA203028 and R01CA201741 to L.Z.,U19AI068021 and R01CA215481 to J.Y.,P30CA047904 to the UPMC Hillman Cancer Center).
文摘Emerging evidence suggests that the clinical success of conventional chemotherapy is not solely attributed to tumor cell toxicity,but also results from the restoration of immunosurveillance,which has been largely neglected in the past preclinical and clinical research.Antitumor immune response can be primed by immunogenic cell death(ICD),a type of cell death characterized by cell-surface translocation of calreticulin(CRT),extracellular release of ATP and high mobility group box 1(HMGB1),and stimulation of type I interferon(IFN)responses.Here we summarize recent studies showing conventional chemotherapeutics as ICD inducers,which are capable of modulating tumor infiltrating lymphocytes(TILs)and reactivating antitumor immunity within an immuno-suppressive microenvironment.Such immunological effects of conventional chemotherapy are likely critical for better prognosis of cancer patients.Furthermore,combination of ICD-inducing chemotherapeutics with immunotherapy is a promising approach for improving the clinical outcomes of cancer patients.
基金supported by the Startup Foundation for Junior Faculty,Nankai University(Grant No.:63191439)the National Natural Science Foundation of China(Grant Nos.:32100418,3210040345)+1 种基金The Health Commission Foundation of China(Grant No.:2018ZX10712001-017)the Chongqing Medical College Natural Fund(Grant Nos.:ygz2019302 and ygz2019305).
文摘Epigenomic imbalance drives abnormal transcriptional processes,promoting the onset and progression of cancer.Although defective gene regulation generally affects carcinogenesis and tumor suppression networks,tumor immunogenicity and immune cells involved in antitumor responses may also be affected by epigenomic changes,which may have significant implications for the development and application of epigenetic therapy,cancer immunotherapy,and their combinations.Herein,we focus on the impact of epigenetic regulation on tumor immune cell function and the role of key abnormal epigenetic processes,DNA methylation,histone post-translational modification,and chromatin structure in tumor immunogenicity,and introduce these epigenetic research methods.We emphasize the value of small-molecule inhibitors of epigenetic modulators in enhancing antitumor immune responses and discuss the challenges of developing treatment plans that combine epigenetic therapy and immuno-therapy through the complex interaction between cancer epigenetics and cancer immunology.
