Phenotypic Characterization and Prognostic Impact of CD103+ Tissue-Resident Memory T Cells in Diffuse Large B-cell Lymphoma

Tissue-resident memory T (TRM) cells stably occupy tissues and contribute to immunosurveillance, where they are associated with favorable survival outcomes in solid tumors. Although 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 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 revealed ITGAE-expressing T cells in both malignant and reactive lymph node samples. However, transcriptional profiles differed as a canonical TRM population was exclusively observed in the malignant setting. This TRM cluster was enriched for genes associated with cytotoxicity and activation and was validated in an external cellular indexing of transcriptomes and epitopes by sequencing (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 coculture experiments of CD103+ versus CD103- T cells with autologous CD20+ B cells, in which CD103+ T cells displayed enhanced killing. CD103+ TRM cells in DLBCL represent a prognostically favorable population with an activated/cytotoxic T-cell phenotype.