肿瘤浸润T细胞的曲目是表征有效的抗肿瘤T细胞反应的新兴方法。肿瘤T细胞曲目的寡克隆扩张已经被评估，但是它们与抗肿瘤效应的关联尚不清楚。我们在这里展示，相对较小的克隆构成的肿瘤反应性T细胞曲线的多克隆部分，在接受单克隆抗PD-L1或抗CD4治疗的肿瘤患者中增加，与抗肿瘤效应相关。与此同时，由主要克隆组成的少克隆部分的大小保持不变。此外，多克隆分数在前体耗竭T细胞中得到了丰富，这对于持久的抗肿瘤反应至关重要，并且更依赖于CCR7 +移行性树突状细胞，这些细胞负责在肿瘤引流淋巴结中引导肿瘤反应性T细胞。这些结果表明，不同的肿瘤反应性克隆的扩张（“克隆扩散”）代表了由抗CD4和抗PD-L1治疗诱导的抗肿瘤T细胞反应的特征。

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-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.