Tumor-Distal Mediastinal Lymph Nodes Harbor Tumor-Related Progenitor Exhausted T Cells in Lung Cancer After Neoadjuvant Chemoimmunotherapy

This dataset comprises single-cell sequencing analysis of 28 tissue samples from five lung squamous cell carcinoma (LUSC) patients who received neoadjuvant chemoimmunotherapy. The samples were collected from five distinct anatomical sites: tumor tissue, adjacent normal tissue, tumor-proximal mediastinal lymph nodes (tpMLN), tumor-distal mediastinal lymph nodes (tdMLN), and peripheral blood. The dataset integrates single-cell RNA sequencing (scRNA-seq), single-cell T-cell receptor sequencing (scTCR-seq), and single-cell B-cell receptor sequencing (scBCR-seq) results, revealing similar immune cell compositions between tpMLN and tdMLN, and demonstrating shared clonal lineages between terminally differentiated exhausted CD8+ T lymphocytes (CD8+Tex-term) within the tumor and CD8+Tpex populations in both types of mediastinal lymph nodes. Multiplex immunofluorescence analysis further confirms the presence of TOX+TCF-1+CXCL13+ CD8+Tpex in both tpMLN and tdMLN. Longitudinal clonal tracking at 1, 6, and 18 months post-surgery detects tumor-derived CD8+ Tex-term and CD8+Tpex-related clones in peripheral blood, suggesting that tdMLN perform immunological functions analogous to tpMLN in LUSC antitumor immune responses. These findings provide crucial data supporting the preservation of tdMLN during surgical resection to maintain immune effector cell reserves and postoperative immunological competence.