Functional status and spatial interaction of T cell subsets driven by specific tumor microenvironment correlate with recurrence of non-small cell lung cancer

作者：Liying Yang, Wei Zhang, Jujie Sun, Guanqun Yang, Siqi Cai, Fenghao Sun, Ligang Xing, Xiaorong Sun · 发表于：Frontiers in Immunology · 年份：2023 · DOI：10.3389/fimmu.2022.1022638 · 被引用次数：18 · 研究领域：Cancer Immunotherapy and Biomarkers、Single-cell and spatial transcriptomics、Immunotherapy and Immune Responses

Background The anti-tumoral or pro-tumoral roles of CD4 + and CD8 + T cells typify the complexity of T cell subsets function in cancer. In the non-small cell lung cancer (NSCLC), the density and topology of distinct T cell phenotypes at the tumor center (TC) versus the invasive margin (IM) are largely unknown. Here, we investigated T cell subsets density and distribution within TC and IM regions in NSCLC and its impact on the prognosis. Methods We performed multiplex immunofluorescence using a tissue microarray of samples from 99 patients with locally advanced NSCLC to elucidate the distributions of tumor cell, T cell subpopulations (CD4/conventional CD4/regulatory CD4/CD8/cytotoxic CD8/pre-dysfunctional CD8/dysfunctional CD8), microvessel density (MVD), cancer-associated fibroblasts (CAFs) and hypoxia-inducible factor-1α (HIF-1α) in TC and IM tissues. Cell-to-cell nearest neighbor distances and interactions were analyzed using the phenoptrreports R package. Cox regression was used to evaluate the associations between T cell subsets density and proximity to tumor cells and recurrence-free survival (RFS). Correlations between different cell subsets were examined by Spearman’s or Kruskal-Wallis tests. Results In the locally advanced NSCLC, the proportion of tumor cells and CAFs in IM is lower than in the TC, while MVD, CD4 + , and CD8 + T lymphocytes were increased, and tumor cells were closer to T lymphocytes and their subsets. The density and proximity of CD4 + and CD8 + T ce...