Interdisciplinary Program in Immunology, University of Iowa, Iowa City, IA 52242.
Department of Pathology, University of Iowa, Iowa City, IA 52242; and.
J Immunol. 2020 Mar 15;204(6):1431-1435. doi: 10.4049/jimmunol.1901172. Epub 2020 Feb 12.
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.
癌症的预后通常与肿瘤浸润 CD8 T 细胞的数量相关，但这些细胞中的许多都能识别常见的人类病原体。病原体特异性“旁观者”CD8 T 细胞对肿瘤免疫的贡献在很大程度上仍是未知的。炎症细胞因子足以激活记忆性 CD8 T 细胞并获得效应功能，这表明肿瘤来源的炎症可能有助于病原体特异性 CD8 T 细胞参与肿瘤控制。在这项研究中，我们发现与肿瘤特异性 CD8 T 细胞相反，肿瘤内的病原体特异性初始记忆 CD8 T 细胞无法发挥其效应功能并影响肿瘤进展。然而，具有反复抗原接触史（即四级记忆）的感染诱导的记忆性 CD8 T 细胞对肿瘤来源的炎症更敏感，从而导致其活化、获得效应功能，并更好地控制肿瘤生长。因此，具有更高识别环境炎症刺激能力的记忆性 CD8 T 细胞可以在缺乏同源抗原识别的情况下有助于抗肿瘤免疫。
