<scp>CD8</scp>⁺ T cells in patients with hypopharyngeal squamous cell carcinoma are susceptible to radiation‐induced damage

Radiotherapy (RT) is a commonly used clinical management for hypopharyngeal squamous cell carcinoma (HPSCC), which represents the most unfavorable prognosis among all subtypes of head and neck squamous cell carcinoma. However, radiation may cause lymphopenia, a significantly adverse event with detrimental prognostic implications for patients. While CD8⁺ T cells are vital in tumor immunity, the specific effects of RT on CD8⁺ T cells as well as the underlying mechanisms have not been clearly elucidated. Here we found that subpopulations of peripheral T lymphocytes exhibited differential profiles in patients with HPSCC compared to healthy individuals both pre- and post-irradiation. Importantly, CD8⁺ T cells from HPSCC patients showed greater reduction of cytokine production, more severe proliferation defect, and increased apoptosis compared to those from healthy individuals after in vitro irradiation. Mechanistically, the ATM-Chk2 pathway mediated the enhanced apoptosis of CD8⁺ T lymphocytes from HPSCC patients upon irradiation. Therefore, our study demonstrated that CD8⁺ T cells in patients with HPSCC exhibit a higher susceptibility to radiation-induced damage compared to those in healthy individuals. The ATM-Chk2 pathway represents a potential immunotherapeutic target for safeguarding CD8⁺ T cells in HPSCC patients against radiation-induced apoptosis.