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Peer-reviewedCC BY-NC-ND 4.0Cell Reports Medicine

Characterization of circulating neoantigen-specific T cell responses and public T cell receptors shaping immune memory in Lynch syndrome carriers

  • Fahriye Duzagac1
  • Nan Deng1
  • Jinling Wang1
  • Supriya Nagaraju1
  • Peter Steinberger2
  • Alexandre Reuben3
  • Krishna M. Sinha1
  • Eduardo Vilar1,4
4 affiliations
  1. 1Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
  2. 2Institute of Immunology, Medical University of Vienna, Vienna, Austria
  3. 3Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
  4. 4Department of GI Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
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Abstract

Lynch syndrome (LS), a common inherited genetic condition predisposing to cancer, provides a unique model to study immune surveillance at the earliest stages of tumorigenesis. A hallmark of LS carcinogenesis is the generation of highly immunogenic neoantigens, yet the transcriptomic states of the T cells that recognize them remain poorly understood. Here, we characterize neoantigen-specific T cells from LS carriers using functional assays, single-cell RNA/T cell receptor (TCR) sequencing, and repertoire integration with existing large datasets. Recurrent neoantigens elicit strong immune responses, with neoantigen-specific T cells mediating cytotoxicity against tumor organoids. Single-cell analysis reveals oligoclonal expansions spanning effector and memory states with enrichment for exhausted subsets among cancer survivors and retention of polyfunctional effectors in cancer-free carriers. Cross-cohort analysis identifies public TCR clonotypes in circulation that overlap with pre-cancer and tumor tissue repertoires. Together, these findings define the architecture of circulating neoantigen-specific immune memory in LS and highlight public TCRs as candidates for immune monitoring and immunoprevention.

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Cite

BibTeXRIS
BibTeX
@article{duzagac2026characterization,
  title = {{Characterization of circulating neoantigen-specific T cell responses and public T cell receptors shaping immune memory in Lynch syndrome carriers}},
  author = {Fahriye Duzagac and Nan Deng and Jinling Wang and Supriya Nagaraju and Peter Steinberger and Alexandre Reuben and Krishna M. Sinha and Eduardo Vilar},
  journal = {Cell Reports Medicine},
  year = {2026},
  month = sep,
  doi = {10.1016/j.xcrm.2026.103057},
  url = {https://doi.org/10.1016/j.xcrm.2026.103057},
  note = {CC BY-NC-ND 4.0},
}
RIS
TY  - JOUR
TI  - Characterization of circulating neoantigen-specific T cell responses and public T cell receptors shaping immune memory in Lynch syndrome carriers
AU  - Fahriye Duzagac
AU  - Nan Deng
AU  - Jinling Wang
AU  - Supriya Nagaraju
AU  - Peter Steinberger
AU  - Alexandre Reuben
AU  - Krishna M. Sinha
AU  - Eduardo Vilar
PY  - 2026
DA  - 2026/09/18
JO  - Cell Reports Medicine
DO  - 10.1016/j.xcrm.2026.103057
UR  - https://doi.org/10.1016/j.xcrm.2026.103057
AB  - Lynch syndrome (LS), a common inherited genetic condition predisposing to cancer, provides a unique model to study immune surveillance at the earliest stages of tumorigenesis. A hallmark of LS carcinogenesis is the generation of highly immunogenic neoantigens, yet the transcriptomic states of the T cells that recognize them remain poorly understood. Here, we characterize neoantigen-specific T cells from LS carriers using functional assays, single-cell RNA/T cell receptor (TCR) sequencing, and repertoire integration with existing large datasets. Recurrent neoantigens elicit strong immune responses, with neoantigen-specific T cells mediating cytotoxicity against tumor organoids. Single-cell analysis reveals oligoclonal expansions spanning effector and memory states with enrichment for exhausted subsets among cancer survivors and retention of polyfunctional effectors in cancer-free carriers. Cross-cohort analysis identifies public TCR clonotypes in circulation that overlap with pre-cancer and tumor tissue repertoires. Together, these findings define the architecture of circulating neoantigen-specific immune memory in LS and highlight public TCRs as candidates for immune monitoring and immunoprevention.
SN  - 2666-3791
ER  -