The Efficacy of Curcumin in Reducing Immunosuppressive States of Peripheral Blood Mononuclear Cells Extracted From Oral Squamous Cell Carcinoma Patients: An In Vitro Study.

Background and objectives Prior studies have shown that patients with oral cancer overexpress programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) in cancer cells and immunocompetent lymphocytes. Current immunotherapeutic interventions include antibodies targeting PD-1/PD-L1. This observational, in vitro, cell culture-based study aimed to assess the concentrations of PD-1 and PD-L1 in the peripheral blood mononuclear cells (PBMCs) of patients with oral squamous cell carcinoma (OSCC) and compare their levels with those in healthy controls, both pre- and post-curcumin intervention. This study also compared the soluble fraction of PD-L1 in the serum of patients with that in controls. We aimed to determine a cutoff level for cell surface PD-1/PD-L1 to differentiate between patients and healthy controls, in order to identify potential targets for immunotherapy. Methodology Blood samples (5 mL) were collected from both controls (n=20) and patients (n=20). Of this, 2 mL was used to collect serum samples, and 3 mL was used for isolation and culture of PBMCs. Cells were analyzed pre- and post-intervention with curcumin for PD-1 and PD-L1 expression. Results This study provides relevant data regarding cellular and serum PD-1/PD-L1 levels in patients with OSCC, which were significantly higher than in controls. Intervention with curcumin decreased PD-L1/PD-1 levels, indicating the therapeutic efficacy of curcumin in suppressing immunotolerance in the tumor microenvironment. We also found that cell lysate PD-L1 and PD-1 had a sensitivity of 75% and specificity of 89%, with cutoff values of 0.602 and 5.53 ng/mL for PD-L1 and PD-1, respectively. The receiver operating characteristic (ROC) curve analysis determined that these markers were suitable for OSCC diagnosis and identifying the appropriate cohort for immunotherapy. Conclusions Our study showed that serum and PBMC lysate PD-1 and PD-L1 levels were higher in advanced cancer cases compared to patients with localized disease without metastasis. Curcumin reduced the levels of PD-1 and PD-L1 in PBMC lysates. Further studies and clinical trials are required to gain deeper insights into its utility as an effective chemo adjuvant.