Key Points Pathogen-specific bystander memory CD8 T cells infiltrate tumors in the absence of Ag. 1°M bystander CD8 T cells are relatively inert in the tumor. 4°M bystander cells gain effector functions independent of cognate Ag recognition. Cancer prognosis often correlates with the number of tumor-infiltrating CD8 T cells, but many of these cells recognize pathogens that commonly infect humans. The contribution of pathogen-specific “bystander” CD8 T cells to antitumor immunity remains largely unknown. Inflammatory cytokines are sufficient for memory CD8 T cell activation and gain of effector functions, indicating tumor-derived inflammation could facilitate pathogen-specific CD8 T cells to participate in tumor control. In this study, we show in contrast to tumor-specific CD8 T cells that pathogen-specific primary memory CD8 T cells inside tumor were not able to exert their effector functions and influence tumor progression. However, infection-induced memory CD8 T cells with defined history of repeated Ag encounters (i.e., quaternary memory) showed increased sensitivity to tumor-derived inflammation that resulted in activation, gain of effector functions, and better control of tumor growth. Thus, memory CD8 T cells with heightened ability to recognize environmental inflammatory stimuli can contribute to antitumor immunity in the absence of cognate Ag recognition.

中文翻译：

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前沿技术：缺乏同源抗原识别的病原体特异性 CD8 T 细胞的抗肿瘤免疫

关键点病原体特异性旁观者记忆 CD8 T 细胞在没有 Ag 的情况下浸润肿瘤。1°M 旁观者 CD8 T 细胞在肿瘤中相对惰性。4°M 旁观者细胞获得独立于同源 Ag 识别的效应器功能。癌症预后通常与肿瘤浸润 CD8 T 细胞的数量相关，但其中许多细胞识别通常感染人类的​​病原体。病原体特异性“旁观者”CD8 T 细胞对抗肿瘤免疫的贡献在很大程度上仍然未知。炎症细胞因子足以激活记忆 CD8 T 细胞并获得效应器功能，表明肿瘤衍生的炎症可以促进病原体特异性 CD8 T 细胞参与肿瘤控制。在这项研究中，我们表明，与肿瘤特异性 CD8 T 细胞相比，肿瘤内的病原体特异性初级记忆 CD8 T 细胞无法发挥其效应功能并影响肿瘤进展。然而，感染诱导的记忆 CD8 T 细胞具有明确的重复 Ag 遭遇历史（即，四级记忆）显示出对肿瘤衍生炎症的敏感性增加，从而导致激活、效应子功能的获得和更好地控制肿瘤生长。因此，在缺乏同源 Ag 识别的情况下，具有增强识别环境炎症刺激能力的记忆 CD8 T 细胞可以促进抗肿瘤免疫。四元记忆）显示对肿瘤衍生的炎症的敏感性增加，从而导致激活、效应子功能的获得和更好地控制肿瘤生长。因此，在缺乏同源 Ag 识别的情况下，具有增强识别环境炎症刺激能力的记忆 CD8 T 细胞可以促进抗肿瘤免疫。第四纪记忆）显示对肿瘤衍生的炎症的敏感性增加，从而导致激活、效应子功能的获得和更好地控制肿瘤生长。因此，在缺乏同源 Ag 识别的情况下，具有增强识别环境炎症刺激能力的记忆 CD8 T 细胞可以促进抗肿瘤免疫。