ArticleBritish journal of cancer2026
Systemic activation and tissue infiltration of CD8 + CX3CR1 + T cells in non-small cell lung cancer treated with neoadjuvant immune checkpoint blockade.
Article in British journal of cancer, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundNeoadjuvant immune checkpoint blockade (NA-ICB) shows promise in treating resectable and locally advanced non-small cell lung cancer (NSCLC), yet the specific T cell subtypes that expand and become functionally reactivated remain incompletely characterised.
methodsWe applied single-cell RNA sequencing, TCR repertoire analysis, and flow cytometry to tumour, paired normal lung tissue, and peripheral blood samples from 26 NA-ICB-treated and 14 treatment-naïve NSCLC patients to investigate responsive T cell subtypes, their tissue origins, migration patterns, and phenotype transitions.
resultsCD8 + CX3CR1 + T cells were significantly enriched in responsive tumours, as evidenced by increased proportions (p = 0.0027) and clonal expansion in scRNA-seq, and elevated protein-level frequencies detected by flow cytometry (p = 0.021). Longitudinal analysis revealed proliferation of these cells in peripheral blood post-treatment. Shared TCR clonotypes were identified across blood and tumour samples. Pseudotime analysis indicated differentiation of these cells into exhausted and cytotoxic NK-like CD8 + T cells upon tumour infiltration.
conclusionThese findings suggest that CD8 + CX3CR1 + T cells may represent circulating cytotoxic precursors associated with effective NA-ICB responses, suggesting their potential as predictive biomarkers and therapeutic targets for adoptive cell therapy.
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