Interleukin‑10 (IL‑10) is a highly pleiotropic cytokine that regulates immunological homeostasis through anti‑inflammatory and/or immunostimulatory functions. Moreover, IL‑10 is well known to exert diverse roles in tumor immunology and immunotherapy. The present study investigated the presence of circulating tumor antigen‑specific IL‑10‑producing T cells in patients with head and neck squamous cell carcinoma (HNSCC), and determined factors that may influence the immunodynamics of IL‑10‑producing T cells. In vitro, peripheral blood mononuclear cells (PBMCs) stimulated with the tumor antigens p53 and MAGE‑A4 were evaluated for interferon (IFN)‑γ/IL‑10 production using the IFN‑γ/IL‑10 double‑color enzyme‑linked immunosorbent spot assay. The proportion of T cells expressing immune checkpoint molecules in PBMCs was analyzed using flow cytometry. Of the 18 patients with HNSCC, 2 (11.1%) and 9 (50.0%) exhibited p53‑specific IFN‑γ and IL‑10 production, respectively. Meanwhile, MAGE‑A4‑specific IFN‑γ and IL‑10 production was detected in 4 (28.6%) and 7 (50.0%) of 14 patients. In the p53‑specific responses, IL‑10‑producing T cells were observed in significantly more patients than IFN‑γ producing T cells (P=0.0275). In both CD4⁺ and CD8⁺ T cells, the proportion of T cells expressing lymphocyte activation gene‑3 (Lag‑3) was significantly lower in patients with p53‑specific IL‑10 production than in those without. In certain patients, Lag‑3 blockade enhanced tumor antigen‑specific IL‑10. Taken together, the present study successfully demonstrated that tumor antigen‑specific IL‑10‑producing T cells exist in the peripheral blood of patients with HNSCC and that Lag‑3⁺ T cells may serve an important role in modulating IL‑10‑producing T cells. These findings provide novel insights into the roles of IL‑10 and Lag‑3 in mediating antitumor immune responses.

Related Articles