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April 5, 2026Cancer Research0 citations

Longitudinal and Spatial Heterogeneity of TCR Repertoires in Metastatic Cancer Immunotherapy

Abstract 7424: Longitudinal and spatial heterogeneity of intra-tumoral TCR repertoires during immunotherapy in metastatic cancers

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Authors

AZAsimina ZoitouSVStefan VelculescuGPGavin Pereira

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Overview

This longitudinal study analyzes TCR repertoires in metastatic cancer patients during immunotherapy, implying unique immune responses at the patient level.

Key Points

  • To investigate the spatial and temporal heterogeneity of TCR repertoires during immunotherapy in metastatic cancers.
  • Performed serial and multi-region sampling (n=52 samples) during immunotherapy in 7 patients with metastatic cancer.
  • Conducted bulk TCR sequencing of TCR-β CDR3 regions to analyze the TCR repertoire.
  • Evaluated TCR repertoire similarity using Morisita’s overlap index and clustered TCR clones by antigen specificity.
  • Assessed T cell dynamics and significance of expansions/regressions using Fisher’s exact test.
  • Used VDJDB and CEDAR databases to map TCR clusters to known antigens.
  • Significant TCR repertoire heterogeneity observed between patients, suggesting private TCR landscapes.
  • Higher heterogeneity between primary and metastatic tumor sites within individual patients.
  • Similar T cell dynamics noted in regressing vs. progressing tumors during immunotherapy.
  • Significantly expanded TCR clusters were identified at autopsy sites and could recognize tumor antigens and neoantigens.
  • Identified viral antigen-specific TCRs across patients, contributing to effective immune responses.

Cite This Study

Zoitou et al. (2026) studied this question.

synapsesocial.com/papers/69d1fceba79560c99a0a2ad0https://doi.org/10.1158/1538-7445.am2026-7424
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