Distinct T cell subsets associated with responses to different neoadjuvant treatments in esophageal squamous cell carcinoma.

Favorable neoadjuvant immunochemotherapy (NICT) in esophageal squamous cell carcinoma is linked to preserved CXCL13+ PD-1+ CD8+ T cells and post-treatment enrichment of a progenitor-like CD8Tex_CXCR4 subset.

• Why it matters: It remains unclear how to best integrate immunotherapy with chemoradiotherapy in ESCC, and which intratumoral CD8+ T cell states track with response to different neoadjuvant regimens.
• What they did: The study integrated paired pre- and post-treatment single-cell RNA sequencing and TCR sequencing from ESCC patients receiving NICT, NCRT, or NICRT, then validated the resulting CD8+ T cell programs in public datasets and independent prospective cohorts.
• The result: CRT responders instead show reduced CXCL13+ CD8+ T cells and enrichment of clonally expanded cytotoxic PD-1- CD8Teff_NIBAN1 cells, and murine data suggest radiotherapy limits PD-1+ expansion while anti-PD-1 induction before radiotherapy improves tumor control.

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