γδ T cells are effectors of immunotherapy in cancers with HLA class I defects

DNA mismatch repair deficient (MMR-d) cancers present an abundance of neoantigens that likely underlies their exceptional responsiveness to immune checkpoint blockade (ICB). However, MMR-d colon cancers that evade CD8+ T cells through loss of Human Leukocyte Antigen (HLA) class I-mediated antigen presentation frequently remain responsive to ICB, suggesting the involvement of other immune effector cells. We performed single-cell RNA-sequencing on γδ T cells isolated from five treatment-naive MMR-deficient colon cancers, to invesigate which γδ T cell subsets are present and what their functional characteristics are.

DNA错配修复缺陷（DNA mismatch repair deficient, MMR-d）肿瘤富含新抗原，这大概率是其对免疫检查点阻断（immune checkpoint blockade, ICB）治疗展现出优异应答反应的分子基础。然而，通过丢失人类白细胞抗原（Human Leukocyte Antigen, HLA）I类介导的抗原呈递途径逃逸CD8+ T细胞杀伤的MMR-d结直肠癌，仍常对ICB治疗产生应答，这提示其他免疫效应细胞参与了该应答过程。本研究对从5例初治（treatment-naive）MMR-d结直肠癌中分离得到的γδ T细胞开展了单细胞RNA测序，以探究其中存在的γδ T细胞亚群及其功能特性。