Department of Radiation Oncology, Weill Cornell Medicine, New York, NY, USA.
Department of Radiation Oncology, Taussig Cancer Center, Cleveland Clinic, Cleveland, OH, USA; Center for Immunotherapy and Precision Immuno-Oncology, Cleveland Clinic, Cleveland, OH, USA; National Center for Regenerative Medicine, Cleveland, OH, USA; Case Comprehensive Cancer Center, Cleveland, OH, USA.
Cancer Cell. 2024 Nov 11;42(11):1825-1863. doi: 10.1016/j.ccell.2024.09.010. Epub 2024 Oct 10.
According to the widely accepted "three Es" model, the host immune system eliminates malignant cell precursors and contains microscopic neoplasms in a dynamic equilibrium, preventing cancer outgrowth until neoplastic cells acquire genetic or epigenetic alterations that enable immune escape. This immunoevasive phenotype originates from various mechanisms that can be classified under a novel "three Cs" conceptual framework: (1) camouflage, which hides cancer cells from immune recognition, (2) coercion, which directly or indirectly interferes with immune effector cells, and (3) cytoprotection, which shields malignant cells from immune cytotoxicity. Blocking the ability of neoplastic cells to evade the host immune system is crucial for increasing the efficacy of modern immunotherapy and conventional therapeutic strategies that ultimately activate anticancer immunosurveillance. Here, we review key hallmarks of cancer immune evasion under the "three Cs" framework and discuss promising strategies targeting such immunoevasive mechanisms.
根据广为接受的“三个 E”模型,宿主免疫系统消除恶性细胞前体,并在动态平衡中包含微观肿瘤,防止癌症生长,直到肿瘤细胞获得使免疫逃逸的遗传或表观遗传改变。这种免疫逃避表型源自各种机制,可归入新的“三个 C”概念框架下:(1)伪装,使癌细胞逃避免疫识别,(2)胁迫,直接或间接地干扰免疫效应细胞,(3)细胞保护,使恶性细胞免受免疫细胞毒性。阻断肿瘤细胞逃避宿主免疫系统的能力对于提高现代免疫疗法和传统治疗策略的疗效至关重要,这些策略最终激活抗肿瘤免疫监视。在这里,我们根据“三个 C”框架综述癌症免疫逃避的关键特征,并讨论针对这些免疫逃避机制的有前途的策略。
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