Division of Molecular Regulation of Inflammatory and Immune Diseases, Research Institute for Biomedical Sciences, Tokyo University of Science, Noda, Japan.
Department of Preventive Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Cancer Immunol Res. 2023 Jun 2;11(6):847-862. doi: 10.1158/2326-6066.CIR-22-0517.
The repertoire of tumor-infiltrating T cells is an emerging method for characterizing effective antitumor T-cell responses. Oligoclonal expansion of the tumor T-cell repertoire has been evaluated; however, their association with antitumor effects is unclear. We demonstrate here that the polyclonal fraction of the tumor-reactive T-cell repertoire, consisting of relatively minor clones, increased in tumor-bearing mice treated with monoclonal anti-programmed death-ligand 1 (PD-L1) or anti-CD4, which correlated with antitumor effects. Meanwhile, the size of the oligoclonal fraction consisting of major clones remained unchanged. Moreover, the polyclonal fraction was enriched in progenitor exhausted T cells, which are essential for a durable antitumor response, and was more dependent on CCR7+ migratory dendritic cells, which are responsible for priming tumor-reactive T cells in the tumor-draining lymph nodes. These results suggest that the expansion of diverse tumor-reactive clones ("clonal spreading") represents characteristics of antitumor T-cell responses induced by anti-CD4 and anti-PD-L1 treatment.
肿瘤浸润 T 细胞的库是一种新兴的方法，用于描述有效的抗肿瘤 T 细胞反应。已经评估了肿瘤 T 细胞库的寡克隆扩增；然而，其与抗肿瘤作用的关系尚不清楚。我们在这里证明，在接受单克隆抗程序性死亡配体 1（PD-L1）或抗 CD4 治疗的荷瘤小鼠中，由相对较少的克隆组成的肿瘤反应性 T 细胞库的多克隆部分增加，这与抗肿瘤作用相关。同时，由主要克隆组成的寡克隆部分的大小保持不变。此外，多克隆部分富含祖细胞衰竭 T 细胞，这些细胞对于持久的抗肿瘤反应至关重要，并且更依赖于 CCR7+迁移树突状细胞，这些细胞负责在肿瘤引流淋巴结中引发肿瘤反应性 T 细胞。这些结果表明，多样化的肿瘤反应性克隆的扩增（“克隆扩散”）代表了抗 CD4 和抗 PD-L1 治疗诱导的抗肿瘤 T 细胞反应的特征。
