Serum from patients with oral squamous cell carcinoma remodels the tumor immune escape ecological niche by promoting regulatory T‑cell differentiation and T‑cell exhaustion

Oral squamous cell carcinoma (OSCC) ranks as the sixth most prevalent malignancy worldwide, and is characterized by high morbidity and mortality rates. Elucidating the molecular and cellular mechanisms of tumor‑directed immune escape through ecological niche remodeling is crucial for advancing tumor biotherapy. The serum of patients with Cancer contains not only tumor biomarkers but also immune regulators secreted by immune cells and/or Cancer cells. Notably, the interstitial fluid within the Cancer ecological niche is derived from serum. The cross‑talk between serum and Cancer cells determines the future of Cancer cells, either cell survival or death. The present study revealed that serum from patients with OSCC could remodel the Cancer immune escape ecological niche by promoting antigen‑induced regulatory T‑cell (Treg) differentiation and T‑cell exhaustion. When serum from patients with OSCC was added to a phytohemagglutinin‑stimulated peripheral blood mononuclear cell (PBMC) culture system, the Treg subset was significantly increased compared with that in the culture system treated with fetal bovine serum. Moreover, when the serum of patients with OSCC was added to a PBMC culture system stimulated with tumor antigens, the activation of the CD3⁺ subset was significantly inhibited, and high levels of IL‑4, IL‑10 and TGF‑β were detected in the supernatant; moreover, CD3⁺ T cells expressed high levels of T‑cell immunoglobulin and mucin‑domain containing‑3 and programmed death ligand 1, which is known to induce T‑cell Apoptosis and exhaustion. Finally, the antitumor effect of T cells were significantly decreased. These results indicated that the serum of patients with Cancer can promote the inhibition and exhaustion of antitumor T cells, thereby remodeling the tumor immune escape ecological niche.

T‑cell exhaustion; ecological niche; patients with cancer; regulatory T cells; serum.