Generation and Immuno-inflammatory Checkpoints in Oral Cavity Cancers

Abstract

Oral malignancies are responsible for a considerable portion of cancer-related deaths worldwide. Even though survival rates have increased recently, new treatments are being explored to slow the advancement of the disease and enhance outcomes, especially in cases of oral cavity squamous cell carcinoma (OSCC) and oral potentially malignant diseases (OPMDs). Immunotherapy is a novel therapeutic approach that targets immune checkpoint molecules such as programmed cell death protein-1 (PD-1) and its ligand programmed death-ligand 1 (PD-L1), cytotoxic T-lymphocyte antigen 4, lymphocyte-activated gene 3, and T cell immunoglobulin mucin 3 in order to enhance the host’s immune response against malignancies and impede the growth and metastasis of cancer cells. Accordingly, a systematic review was performed by scanning five databases for keywords related to immune checkpoint inhibitors, along with oral malignancies, oral pathologies, and OPMDs, in order to describe the current state of their use and efficacy in these disorders. For this purpose, 644 unique publications published between 2004 and 2019 were found, 76 of which were judged to be appropriate for the study and produced 8826 samples. PD-1 and PD-L1 are expressed in most OPMD and OSCC samples, and their expression is associated with worse survival rates and greater rates of progression. Two immunotherapy drugs targeting PD-1, namely, pembrolizumab and nivolumab, have been demonstrated to enhance disease outcomes and increase survival rates, especially when combined with radiation or chemotherapy. Despite the equivocal nature of the available data, there is support for the prognostic and predictive usefulness of immune checkpoint molecules, notably PD-L1, and multiple studies support the useful use of immune checkpoint inhibitors in the management of OSCC.