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Overcoming immunotherapeutic resistance by targeting the cancer inflammation cycle.
Seminars in Cancer Biology ( IF 12.1 ) Pub Date : 2020-01-15 , DOI: 10.1016/j.semcancer.2020.01.002
Max M Wattenberg 1 , Gregory L Beatty 1
Affiliation  

Inflammation is a hallmark of cancer and supports tumor growth, proliferation, and metastasis, but also inhibits T cell immunosurveillance and the efficacy of immunotherapy. The biology of cancer inflammation is defined by a cycle of distinct immunological steps that begins during disease conception with the release of inflammatory soluble factors. These factors communicate with host organs to trigger bone marrow mobilization of myeloid cells, trafficking of myeloid cells to the tumor, and differentiation of myeloid cells within the tumor bed. Tumor-infiltrating myeloid cells then orchestrate an immunosuppressive microenvironment and assist in sustaining a vicious cycle of inflammation that co-evolves with tumor cells. This Cancer-Inflammation Cycle acts as a rheostat or “inflammostat” that impinges upon T cell immunosurveillance and prevents the development of productive anti-tumor immunity. Here, we define the major nodes of the Cancer-Inflammation Cycle and describe their impact on T cell immunosurveillance in cancer. Additionally, we discuss emerging pre-clinical and clinical data suggesting that intervening upon the Cancer-Inflammation Cycle will be a necessary step for broadening the potential of immunotherapy in cancer.



中文翻译:

通过靶向癌症炎症周期克服免疫治疗耐药性。

炎症是癌症的标志,支持肿瘤生长、增殖和转移,但也抑制 T 细胞免疫监视和免疫治疗的功效。癌症炎症的生物学定义为不同免疫学步骤的循环,该循环在疾病受孕期间随着炎性可溶性因子的释放而开始。这些因子与宿主器官交流以触发骨髓细胞的骨髓动员、骨髓细胞向肿瘤的运输以及肿瘤床内骨髓细胞的分化。肿瘤浸润的骨髓细胞然后协调免疫抑制微环境并协助维持与肿瘤细胞共同进化的炎症的恶性循环。这种癌症 - 炎症循环充当变阻器或“炎症抑制剂”,它会影响 T 细胞免疫监视并阻止生产性抗肿瘤免疫的发展。在这里,我们定义了癌症-炎症循环的主要节点,并描述了它们对癌症中 T 细胞免疫监视的影响。此外,我们讨论了新出现的临床前和临床数据,表明干预癌症-炎症循环将是扩大癌症免疫疗法潜力的必要步骤。

更新日期:2020-01-15
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