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Jain A, Verma S, Jadhav A, John S, Gupta S. Role of nanotechnology in modulating the tumor microenvironment to enhance immunotherapy efficacy. World J Clin Oncol 2026; 17(1): 111294 [PMID: 41608337 DOI: 10.5306/wjco.v17.i1.111294]
Ayushi Jain, Department of Dentistry, Kalyan Singh Government Medical College, Bulandshahr 203001, Uttar Pradesh, India
Saloni Verma, Sharon John, Shalini Gupta, Department of Oral Pathology and Microbiology, King George’s Medical University, Lucknow 226003, Uttar Pradesh, India
Alisha Jadhav, Department of Paediatric and Preventive Dentistry, King George’s Medical University, Lucknow 226003, Uttar Pradesh, India
Author contributions: Jain A and Verma S reviewed the literature and wrote the original draft; Jadhav A, John S, and Gupta S validated and analyzed the results; All authors read and approved the final version of the manuscript.
Conflict-of-interest statement: The authors declare that they have no known conflict of interest.
Corresponding author: Shalini Gupta, PhD, Full Professor, Head, Department of Oral Pathology and Microbiology, King George’s Medical University, Shah Mina Road, Lucknow 226003, Uttar Pradesh, India. dr.shalni@gmail.com
Received: June 27, 2025 Revised: August 14, 2025 Accepted: November 20, 2025 Published online: January 24, 2026 Processing time: 207 Days and 18.2 Hours
Core Tip
Core Tip: Oral squamous cell carcinoma exhibits a highly immunosuppressive tumor microenvironment (TME) that severely limits immunotherapy efficacy. This review highlighted how nanotechnology offers transformative strategies to overcome key TME barriers. Specifically, engineered nanoparticles can reprogram tumor-associated macrophages, alleviate hypoxia via oxygen-generating carriers, disrupt cancer-associated fibroblasts and extracellular matrix, and deliver targeted therapies (e.g., human papillomavirus E6/E7 small interfering RNA). Oral squamous cell carcinoma-tailored approaches also counteract carcinogen-induced oxidative stress and microbiota-driven immunosuppression. These innovations enable precise TME remodeling to enhance immune cell infiltration and checkpoint inhibitor performance, representing a paradigm shift towards improving clinical outcomes in oral cancer immunotherapy.
