Background The tumor necrosis factor receptor superfamily, member 4 (OX40) and its ligand (OX40L) are members of the tumor necrosis factor superfamily and play roles as costimulatory immunomodulators to combat infectious diseases as well as cancers. Presently, many therapeutic agents focused on OX40 and OX40L are in trials for antitumor efficacy. In Pakistan, oral squamous cell carcinoma (OSCC) is the second most prevalent cancer with a mortality of 50% despite the availability of various therapeutic modalities. Data regarding serum levels of OX40 in patients with OSCC is lacking. Therefore, the study aimed to assess the OX40 levels in serum and their association with the clinicopathological features of the tumor. Methodology A cross-sectional study was conducted and serum samples of 78 biopsy-confirmed OSCC patients were collected prior to any treatment along with 10 healthy persons after informed consent. Serum levels of OX40 were measured via sandwich enzyme-linked immunosorbent assay (ELISA). Results The mean serum levels of OX40 were 1.65 ± 0.64 ng/ml and 2.39 ± 0.58 ng/ml in early and late-stage disease patients of OSCC, respectively (p =<0.005). However, based on gender and tumor site, male gender and buccal mucosa tumors in late-stage OSCC patients showed higher mean levels of OX40, 2.42± 0.58 ng/ml and 2.41 ± 0.58 ng/ml (p =<0.05), respectively. Patients with well-differentiated tumors demonstrated mean serum levels of 2.28 ng/ml, and in moderately differentiated tumors, the mean levels were 2.19 ng/ml (p =0.47). Conclusions A high OX40 level is associated with advanced-stage disease and a poor prognosis, possibly reflecting the immune-exhausted status against OSCC.
Keywords: cancer; immune checkpoints; immunotherapy; oral squamous cell carcinoma; ox40.
Copyright © 2021, Sani et al.