Precision immuno-oncology in oral cancer: latest trends in biomarkers, novel drug development and nanoparticle-based therapeutic platforms

Oral squamous cell carcinoma poses a significant global health burden, with over 370,000 annual cases and poor 5-year survival rates of 50%-60%, driven by risk factors like tobacco and alcohol. Despite advances in surgery, radiotherapy, and chemotherapy, functional morbidity and resistance necessitate precision immuno-oncology approaches. This review explores the tumour immune microenvironment in oral squamous cell carcinoma, characterized by immunosuppressive elements like M2 macrophages, myeloid-derived suppressor cells, and regulatory T cells, alongside spatial heterogeneity that complicates therapy. Biomarkers for patient selection include programmed death-ligand1 expression (via combined positive scoring), tumour mutational burden, neoantigen load, interferon-gamma-γ signatures, cytolytic scores, peripheral circulating tumour DNA, and single-cell/spatial profiling, though standardization remains critical. Immunotherapy has transformed oral squamous cell carcinoma management, with programmed cell death protein-1 inhibitors like nivolumab and pembrolizumab showing survival benefits in trials, particularly in programmed cell death protein-L1-positive cases. Emerging strategies encompass next-generation checkpoints (Lymphocyte activation gene-3, T-cell immunoreceptor with Ig and ITIM domains, OX40), personalized neoantigen vaccines, adoptive cell therapies (Tumour-Infiltrating Lymphocytes, Chimeric Antigen Receptor T-cell therapy), and rational combinations to counter resistance. Nanomedicine platforms-liposomes, polymeric nanoparticles, gold-based systems-enhance drug delivery, reprogram the Tumour and immune microenvironment, and enable chemo-immuno-photothermal synergies, addressing mucosal barriers and toxicity. Future priorities include biomarker validation via prospective registries, scalable Good Manufacturing Practice nanoplatforms, AI-driven multi-omic modeling, and federated learning for predictive analytics. By integrating tumour genomics, immune profiling, and advanced delivery, precision immuno-oncology holds promise to improve response rates, durability, and quality of life in oral squamous cell carcinoma.