Review discusses complexity of immune-suppressive mechanisms in tumor milieu of cancers

Cancers control immune systems and evade immune detection using mediators consisting of immune checkpoint molecules and cellular systems associated with immune suppression.

In this review, the complexity of immune-suppressive mechanisms in the tumor milieu of cancers, including oral malignancy is discussed in relation to immune check point inhibitors, regulatory T cells (Treg), myeloid-derived suppressor cells (MDSCs) and cancer-associated fibroblasts (CAFs). In addition, the therapeutic approach of oral pre-cancerous disorders is mentioned. Some reports also advocate that the immunosuppressive efficacy of the oral squamous cell carcinoma (OSCC) milieu is developed in a stepwise manner depending on the stages of OSCCs. Namely, in the early stage, CAFs could be a unique effector; humoral factor(s) from OSCC cells force CAF to exert immune suppression via the direct cell contacts to effector T cells. Potentiated CAF could also affect other immune-suppressive mediators such as Treg, tumor-associated macrophages (TAMs) and MDSCs. In the advanced stage of OSCC, MDSCs could possibly be a major conductor of immune-suppression. However, how OSCCs differentially utilize the immune modulatory aspects involving CAFs, MDSCs and several other factors is not fully understood. Further elucidation of the regulatory pathways structured by tumor-host interactions could identify important therapeutic targets in OSCC development.