Therapy by adoptive transfer of ex vivo-expanded tumor-infiltrating or genetically modified T cells may lead to impressive clinical responses. However, there is a need to improve in vivo persistence and functionality of the transferred T cells, in particular, to face the highly immunosuppressive environment of solid tumors. Here, we investigate the potential of miR-155, a microRNA known to play an important role in CD8⁺ T cell fitness. We show that forced expression of miR-155 in tumor antigen-specific T cells improves the tumor control of B16 tumors expressing a low-affinity antigen ligand. Importantly, miR-155-transduced T cells exhibit increased proliferation and effector functions associated with a higher glycolytic activity independent of exogenous glucose. Altogether, these data suggest that miR-155 may optimize the antitumor activity of adoptively transferred low-affinity tumor-infiltrating lymphocytes (TILs), in particular, by rendering them more resistant to the glucose-deprived environment of solid tumors. Thus, transgenic expression of miR-155 may enable therapeutic targeting of self-antigen-specific T cells in addition to neoantigen-specific ones.

通过过继转移离体扩展的肿瘤浸润或基因修饰的T细胞进行治疗可能会引起令人印象深刻的临床反应。然而，需要改善转移的T细胞的体内持久性和功能，特别是面对实体瘤的高度免疫抑制环境。在这里，我们研究了miR-155（一种在CD8 ^+中起重要作用的微小RNA）的潜力T细胞健康。我们表明，miR-155在肿瘤抗原特异性T细胞中的强制表达改善了表达低亲和力抗原配体的B16肿瘤的肿瘤控制。重要的是，miR-155转导的T细胞表现出增加的增殖和效应功能，与更高的糖酵解活性相关，而与外源葡萄糖无关。总而言之，这些数据表明，miR-155可以优化过继转移的低亲和力的肿瘤浸润淋巴细胞（TIL）的抗肿瘤活性，特别是通过使它们对实体瘤的葡萄糖剥夺环境更具抵抗力。因此，除了新抗原特异性的细胞外，miR-155的转基因表达还可以治疗性靶向自身抗原特异性的T细胞。