Cancer-induced immunosuppressive cascades and their reversal by molecular-targeted therapy.
Cancer-induced immunosuppressive cascades and their reversal by molecular-targeted therapy.
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癌症引起的免疫抑制级联反应及其通过分子靶向治疗的逆转。
DOI：
10.1111/nyas.12094
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Kawamura N
中科院分区：
文献类型：
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作者：
Kawakami Y;Yaguchi T;Sumimoto H;Kudo-Saito C;Tsukamoto N;Iwata-Kajihara T;Nakamura S;Nishio H;Satomi R;Kobayashi A;Tanaka M;Hoon Park J;Kamijuku H;Tsujikawa T;Kawamura N
肿瘤组织的免疫状态因患者而异。记忆型 CD8+T 细胞向肿瘤的浸润与各种癌症患者的预后相关。然而，差异性CD8+T细胞浸润的机制尚未得到很好的研究。一般来说，肿瘤相关的微环境，包括肿瘤和前哨淋巴结，处于免疫抑制条件下，如果没有免疫激活干预，免疫系统无法消除癌细胞。人类癌细胞中各种信号通路的组成性激活会触发涉及各种细胞因子、趋化因子和免疫抑制细胞的多种免疫抑制级联反应。信号通路抑制剂可以通过作用于癌症或免疫细胞或两者来抑制这些免疫抑制级联反应。此外，常见的信号传导机制通常用于癌症的多个特征（例如细胞增殖/存活、侵袭/转移和免疫抑制）。因此，针对这些常见的信号通路可能是包括免疫疗法在内的癌症治疗的一个有吸引力的策略。
Immunological status in tumor tissues varies among patients. Infiltration of memory‐type CD8+T cells into tumors correlates with prognosis of patients with various cancers. However, the mechanism of the differential CD8+T cell infiltration has not been well investigated. In general, tumor‐associated microenvironments, including tumor and sentinel lymph nodes, are under immunosuppressive conditions such that the immune system is not able to eliminate cancer cells without immune‐activating interventions. Constitutive activation of various signaling pathways in human cancer cells triggers multiple immunosuppressive cascades that involve various cytokines, chemokines, and immunosuppressive cells. Signaling pathway inhibitors could inhibit these immunosuppressive cascades by acting on either cancer or immune cells, or both. In addition, common signaling mechanisms are often utilized for multiple hallmarks of cancer (e.g., cell proliferation/survival, invasion/metastasis, and immunosuppression). Therefore, targeting these common signaling pathways may be an attractive strategy for cancer therapy including immunotherapy.