Divergent immuno-landscapes: comparing the tumor microenvironment of Indian and Western HNSCC patients

Head and neck squamous cell carcinoma (HNSCC) is a highly dynamic and heterogeneous cancer where the tumor microenvironment (TME) and immune landscape differ across populations. Western groups often show an "immune-hot" profile with infiltration by various immune cells, including cytotoxic CD8⁺ T cells, helper CD4⁺ T cells, and regulatory T cells. In contrast, Indian groups frequently display an inflammation-rich yet immunosuppressive microenvironment dominated by myeloid cells. The Asian population, particularly Indian patients, often exhibits distinct immune subtypes influenced by region-specific factors such as tobacco and areca nut use, rather than smoking and alcohol. Indian oral squamous cell carcinoma (OSCC) of the gingivobuccal region shows unique distributions and functional states of antitumor immune populations, with differences in activation and suppression signatures that impact prognosis, metastasis, and treatment response. Major Histocompatibility Complex (MHC) molecules are essential for the immunotherapeutic response, and studies have reported the influence of specific Human Leukocyte Antigen (HLA) class I and II gene variants on antigen presentation and T cell activation. These allelic variants may serve as indicators of tumor microenvironment (TME) involvement and could affect the effectiveness of immunotherapy. Recognizing population-specific variations in immune cell infiltration highlights biological differences in carcinogenesis and offers opportunities to discover new biomarkers and stratify patients for personalized treatment strategies.