Spatial distribution of tumor-infiltrating T cells indicated immune response status under chemoradiotherapy plus PD-1 blockade in esophageal cancer

Frontiers in Immunology

Immunology

Fuliang Cao¹  Peng Tang²  Hongjing Jiang²  Cihui Yan³  Meng Wang⁴  Jie Dong⁵  Gang Zhao⁶  Tian Zhang⁷  Hui Huang⁷  Ping Wang⁷  Xiaoxue Ma⁷  Wencheng Zhang⁷  Zhunhao Zheng⁷  Xi Chen⁷  Qingsong Pang⁷  Hui Wei⁷ 

[1]Department of Endoscopy Diagnosis and Therapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin, China

[2]Department of Esophageal Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin, China

[3]Department of Immunology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Immunology and Biotherapy, Tianjin’s Clinical Research Center for Cancer, Tianjin, China

[4]Department of Lung Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin, China

[5]Department of Nutrition Therapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin, China

[6]Department of Pathology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin, China

[7]Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin, China

关键词: esophageal squamous cell carcinoma;    spatial analysis;    immunotherapy;    chemoradiotherapy;    PD-1;    tumor-infiltrating T cell;   

DOI  :  10.3389/fimmu.2023.1138054

 received in 2023-01-05, accepted in 2023-05-04,  发布年份 2023

来源: Frontiers

【 摘 要 】

BackgroundThe spatial distribution of tumor-infiltrating T cells and its dynamics during chemoradiotherapy combined with PD-1 blockade is little known in esophageal squamous cell carcinoma (ESCC).MethodsWe applied the multiplex immunofluorescence method to identify T cells (CD4+, CD8+ T cells, and their PD-1− or PD-1+ subsets) and myeloid-derived cells (CD11c+ dendritic cells, CD68+ macrophages, and their PD-L1+ subpopulations) in paired tumor biopsies (n = 36) collected at baseline and during combination (40 Gy of radiation) from a phase Ib trial (NCT03671265) of ESCC patients treated with first-line chemoradiotherapy plus anti-PD-1 antibody camrelizumab. We used the FoundationOne CDx assay to evaluate tumor mutational burden (TMB) in baseline tumor biopsies (n = 14). We dynamically assessed the nearest distance and proximity of T-cell subsets to tumor cells under combination and estimated the association between T-cell spatial distribution and combination outcome, myeloid-derived subsets, TMB, and patient baseline characteristics.FindingsWe found that the tumor compartment had lower T-cell subsets than the stromal compartment but maintained a comparable level under combination. Both before and under combination, PD-1− T cells were located closer than PD-1+ T cells to tumor cells; T cells, dendritic cells, and macrophages showed the highest accumulation in the 5–10-μm distance. Higher CD4+ T cells in the tumor compartment and a shorter nearest distance of T-cell subsets at baseline predicted poor OS. Higher baseline CD4+ T cells, dendritic cells, and macrophages were associated with worse OS in less than 10-μm distance to tumor cells, but related with better OS in the farther distance. Higher on-treatment PD-1-positive-expressed CD4+ and CD8+ T cells within the 100-μm distance to tumor cells predicted longer OS. T cells, dendritic cells, and macrophages showed a positive spatial correlation. Both high TMB and smoking history were associated with a closer location of T cells to tumor cells at baseline.ConclusionsWe firstly illustrated the T-cell spatial distribution in ESCC. Combining chemoradiotherapy with PD-1 blockade could improve the antitumor immune microenvironment, which benefits the treatment outcome. Further understanding the precision spatiality of tumor-infiltrating T cells would provide new evidence for the tumor immune microenvironment and for the combination treatment with immunotherapy.

【 授权许可】

Unknown   
Copyright © 2023 Yan, Huang, Zheng, Ma, Zhao, Zhang, Chen, Cao, Wei, Dong, Tang, Jiang, Wang, Wang, Pang and Zhang