Work

Analysis of the TCRβ repertoire characteristics when combining radiotherapy and immunotherapy in cancer

Year: 2025

Type: article

Abstract: Cancer is a global public health concern. Radiotherapy (RT) and immunotherapy are increasingly used in cancer treatment, but the specific immune mechanisms underlying their effects remain to be elucidated. The present study analyzed publicly available datasets, in which the T-cell receptor β chain (TCRβ) repertoire in tumor-bearing mice treated with RT and immunotherapy, as well as the TCR repertoire of T cells derived from hematopoietic stem cells (HSCs) of mice exposed to radiation doses of 0, 10 and 100 mGy were comprehensively evaluated. The results of the present study indicated that the diversity of the TCRβ complementarity-determining region 3 (CDR3) in tumor-bearing mice decreased after RT, anti-cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) and anti-programmed cell death protein-1 (PD-1) treatment, especially in the RT and RT + anti-CTLA-4 or anti-PD-1 treatment groups. Furthermore, the CDR3 length markedly decreased in the RT group and markedly increased in the anti-CTLA-4 and anti-PD-1 groups. Next, the TCR profile of T cells differentiated from HSCs exposed to different radiation doses was examined. As the radiation dose increased, the TCRβ diversity in mice gradually decreased and the degree of clonal expansion markedly increased, the percentage of private sequences (unique sequences detected in only a single mouse) was markedly increased and the degree of overlap was markedly decreased. Furthermore, there was a notable difference in the usage frequency of TCRβ chain variable/joining gene segments among the different radiation dose groups. The present study demonstrated that RT and immunotherapy may alter the TCR repertoire owing to their effects on HSCs.

Source: Oncology Letters

DOI: 10.3892/ol.2025.15420