Abstract A040: Measurement of CD8+ T cell-mediated anti-tumor immune response induced by neoadjuvant chemo-radiation therapy using T-cell receptor analysis in rectal cancer patient

Abstract Neoadjuvant chemo-radiation therapy (CRT) is a standard treatment option for patients with advanced rectal cancer. Recent evidences suggested that CRT not only exerts a cytotoxic activity against tumor cells, but also elicits anti-tumor immune response by inducing immunologic cell death (ICD). To evaluate the role of CRT on anti-tumor immune response, we examined the change of peripheral CD8+ T cell clonotypes during and after neoadjuvant CRT. We isolated peripheral blood mononuclear cells (PBMCs) from rectal cancer patients at five different time points: (1) the onset of CRT, (2) two weeks after the onset of CRT, (3) one month after the onset of CRT, (4) one month after CRT termination, (5) just before surgery. To measurement CD8+ T cell-mediated anti-tumor immune response, we sorted CD8+ T cell into various CD8+ T cell subpopulations and performed RNA-based bulk T-cell receptor (TCR) sequencing. We tracked the change of CD8+ T cell clonotypes during and after neoadjuvant CRT. Among various CD8+ T cell subpopulations including naïve (TN), central memory (TCM), effector memory (TEM), and terminally differentiated effector memory T cell (TEMRA) cells, the clonal repertoire of TEM cells, which has been considered to be related to anti-tumor immune response, changed most. The change of TEM clonotypes repertoire was remarkable after the termination of CRT. Especially, novel TEM clonotypes, which had not been detected in peripheral blood at the start of CRT, emerged after the termination of CRT, suggesting the possibility that CRT induced the neoantigen exposure by ICD of cancer cells and novel CD8+ T cell clones were primed by the exposed neoantigens. We first identified the clonal change of peripheral CD8+ T cell elicited by neoadjuvant CRT in rectal cancer patients. Future studies that investigate the relevance of the novel CD8+ T cell clones to anti-tumor immune response and examine the potential of immunotherapy in rectal cancer patients receiving CRT are warranted. Citation Format: YONG JOON LEE, Jae Hyung Jeong, Jin Hee Yeo. Measurement of CD8+ T cell-mediated anti-tumor immune response induced by neoadjuvant chemo-radiation therapy using T-cell receptor analysis in rectal cancer patient [abstract]. In: Proceedings of the AACR Immuno-Oncology Conference (AACR IO): Discovery and Innovation in Cancer Immunology: Revolutionizing Treatment through Immunotherapy; 2026 Feb 18-21; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Immunol Res 2026;14(2 Suppl):Abstract nr A040.