Cancer Immunol Res. 2025 Nov 21. doi: 10.1158/2326-6066.CIR-25-0445. Online ahead of print.

ABSTRACT

Tissue-resident memory T (TRM) cells, memory T cells that stably occupy tissues and contribute to immunosurveillance, induce favorable survival outcomes in solid tumors. While TRM cells have been observed in lymph nodes, their phenotype and prognostic significance in diffuse large B-cell lymphoma (DLBCL) remains uncharacterized. In this study, CD103+ T cells were quantified in DLBCL samples by immunofluorescence (IF) staining of tissue biopsies and flow cytometry of cell disaggregates, and linked with clinical outcomes. Across two patient cohorts, CD103+ T cells were identified in both nodal and extranodal DLBCL, and higher CD103+ T cell levels correlated with superior clinical outcomes. Single-cell RNA sequencing (scRNAseq) revealed ITGAE expressing T cells in both malignant and reactive lymph node (rLN) samples. However, transcriptional profiles differed, as a canonical TRM population was observed in the malignant setting. This TRM cluster was enriched for genes associated with cytotoxicity and activation and was validated in an external CITEseq dataset. Flow cytometry additionally confirmed protein expression of TRM markers (CXCR6, CD39, and PD-1) on CD69+CD103+ T cells. We assessed functional activity in co-culture experiments of CD103+ versus CD103- T cells with autologous CD20+ B cells, where CD103+ T cells displayed enhanced killing. CD103+ TRM cells in DLBCL represent a prognostically favorable population with an activated/cytotoxic T cell phenotype.

PMID:41270222 | DOI:10.1158/2326-6066.CIR-25-0445