Tumor antigen‑specific interleukin‑10‑producing T‑cell response in patients with head and neck squamous cell...

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.