X-ray-induced more serious damage to CD8+ T cells in patients with hypopharyngeal squamous cell carcinoma (HPSCC) than those in healthy individuals

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 of healthy individuals after in vitro irradiation. Mechanistically, ATM-Chk2 pathway mediated the attenuated radiation-induced apoptosis of CD8+ T lymphocytes from HPSCC patients. Our study demonstrated that CD8+ T cells in patients with HPSCC are more sensitive to the radiation-induced damage than those in healthy individuals. Therefore, our findings present a potential immunotherapeutic target for safeguarding CD8+ T cells against radiation-induced damage. Overall design: Peripheral blood mononuclear cells (PBMCs) were extracted using Ficoll density gradient centrifugation. CD8+ T lymphocytes were isolated with EasySepTM human whole blood CD8 positive selection kit (STEMCELL) according to the manufacturer's instructions. CD8+ T cells were untreated or irradiated at the dose of 2 Gy within an X-ray irradiator (RS2000, Rad Source, Georgia) in a dose equivalent time frame. Cells were harvested for RNA sequencing after 24 hours.