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

Area of Science:

• Immunology
• Oncology
• Cell Biology

Background:

• Tissue-resident memory T (TRM) cells are crucial for immunosurveillance and improve outcomes in solid tumors.
• The role and characteristics of TRM cells in diffuse large B-cell lymphoma (DLBCL) are not well understood.

Purpose of the Study:

• To investigate the phenotype, prognostic significance, and functional activity of CD103+ T cells, specifically TRM cells, in DLBCL patients.
• To determine if CD103+ T cells in DLBCL exhibit a canonical TRM phenotype and correlate with clinical outcomes.

Main Methods:

• Immunofluorescence (IF) staining and flow cytometry were used to quantify CD103+ T cells in DLBCL tissue biopsies and cell disaggregates.
• Single-cell RNA sequencing (scRNAseq) and CITEseq were employed to analyze the transcriptional profiles and identify TRM populations.
• Co-culture experiments assessed the cytotoxic activity of CD103+ T cells against autologous CD20+ B cells.

Main Results:

• Higher levels of CD103+ T cells were found in both nodal and extranodal DLBCL and correlated with superior clinical outcomes.
• scRNAseq identified a distinct TRM population in DLBCL, enriched for cytotoxicity and activation genes, validated by CITEseq.
• CD103+ T cells demonstrated enhanced killing capacity compared to CD103- T cells in co-culture assays.

Conclusions:

• CD103+ TRM cells in DLBCL represent a prognostically favorable population.
• These cells possess an activated/cytotoxic T cell phenotype, contributing to anti-tumor immunity.
• The findings highlight the potential of targeting TRM cells for improved DLBCL treatment strategies.