Tumor-associated Tregs obstruct anti-tumor immunity by promoting T cell dysfunction and restricting clonal diversity in tumor-infiltrating CD8+ T cells

We investigated how accumulation of Tregs contributes to T cell dysfunction and clonal constriction of tumor-infiltrating CD8+ T cells. Resected melanoma atissues from tumor-bearing mice were analyzed. The clonal diversity of tumor-associated CD8+ T cells were evaluated by single-cell TCR sequencing respectively, at early or advanced tumor stages or under Treg depletion conditions. TCR-sequencing revealed a clonal shrinkage of tumor-infiltrating CD8+ T cells as tumor progressed, which was associated with reduced survival profile concomitant to increasing Treg proportions. CD8+ T cells sorted from melanoma tissues in B16-F10 incoculated mice were processed for single-cell TCR sequencing