Department of Laboratory Medicine, Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Institute of Biliary Tract Diseases Research, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Nat Commun. 2020 Dec 8;11(1):6268. doi: 10.1038/s41467-020-20019-0.
Cancer immunotherapy has revolutionized cancer treatment, and it relies heavily on the comprehensive understanding of the immune landscape of the tumor microenvironment (TME). Here, we obtain a detailed immune cell atlas of esophageal squamous cell carcinoma (ESCC) at single-cell resolution. Exhausted T and NK cells, regulatory T cells (Tregs), alternatively activated macrophages and tolerogenic dendritic cells are dominant in the TME. Transcriptional profiling coupled with T cell receptor (TCR) sequencing reveal lineage connections in T cell populations. CD8 T cells show continuous progression from pre-exhausted to exhausted T cells. While exhausted CD4, CD8 T and NK cells are major proliferative cell components in the TME, the crosstalk between macrophages and Tregs contributes to potential immunosuppression in the TME. Our results indicate several immunosuppressive mechanisms that may be simultaneously responsible for the failure of immuno-surveillance. Specific targeting of these immunosuppressive pathways may reactivate anti-tumor immune responses in ESCC.
癌症免疫疗法已经彻底改变了癌症的治疗方式，它在很大程度上依赖于对肿瘤微环境（TME）免疫景观的全面理解。在这里，我们以单细胞分辨率获得了食管鳞状细胞癌（ESCC）的详细免疫细胞图谱。衰竭的 T 和 NK 细胞、调节性 T 细胞（Tregs）、交替激活的巨噬细胞和耐受原性树突状细胞在 TME 中占主导地位。转录谱分析结合 T 细胞受体（TCR）测序揭示了 T 细胞群中的谱系联系。CD8 T 细胞表现出从预耗竭到耗竭 T 细胞的连续进展。虽然衰竭的 CD4、CD8 T 和 NK 细胞是 TME 中主要的增殖细胞成分，但巨噬细胞和 Tregs 之间的相互作用有助于 TME 中的潜在免疫抑制。我们的结果表明了几种可能同时导致免疫监视失败的免疫抑制机制。针对这些免疫抑制途径的特异性靶向可能会在 ESCC 中重新激活抗肿瘤免疫反应。
