Immunology Program, Moffitt Cancer Center, Tampa, Florida.
Cutaneous Oncology Program, Moffitt Cancer Center, Tampa, Florida.
Cancer Immunol Res. 2019 Nov;7(11):1837-1848. doi: 10.1158/2326-6066.CIR-19-0229. Epub 2019 Aug 28.
STING (stimulator of IFN genes) signaling is an innate immune pathway for induction of a spontaneous antitumor T-cell response against certain immunogenic tumors. Although antigen-presenting cells are known to be involved in this process, insight into the participation of tumor cell-intrinsic STING signaling remains weak. In this study, we find diversity in the regulation of STING signaling across a panel of human melanoma cell lines. We show that intact activation of STING signaling in a subset of human melanoma cell lines enhances both their antigenicity and susceptibility to lysis by human melanoma tumor-infiltrating lymphocytes (TIL) through the augmentation of MHC class I expression. Conversely, defects in the STING signaling pathway protect melanoma cells from increased immune recognition by TILs and limit their sensitivity to TIL lysis. Based on these findings, we propose that defects in tumor cell-intrinsic STING signaling can mediate not only tumor immune evasion but also resistance to TIL-based immunotherapies.
STING（干扰素基因刺激物）信号是诱导针对某些免疫原性肿瘤的自发抗肿瘤 T 细胞反应的先天免疫途径。尽管已知抗原呈递细胞参与了这一过程，但对肿瘤细胞内在的 STING 信号的参与仍知之甚少。在这项研究中，我们发现了一系列人黑色素瘤细胞系中 STING 信号调节的多样性。我们表明，在人类黑色素瘤细胞系的亚群中，完整的 STING 信号激活通过增强 MHC Ⅰ类表达，增强了它们的抗原性和对人类黑色素瘤肿瘤浸润淋巴细胞（TIL）的溶解敏感性。相反，STING 信号通路的缺陷可保护黑色素瘤细胞免受 TIL 增强的免疫识别，并限制其对 TIL 溶解的敏感性。基于这些发现，我们提出肿瘤细胞内在的 STING 信号缺陷不仅可以介导肿瘤免疫逃逸，还可以抵抗基于 TIL 的免疫疗法。
