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Advances and challenges in cancer immunotherapy: mechanisms, clinical applications, and future directions

Neeharika Vatsavai,Sumeet Kaur Bhinder,Rahaman Shaik,Shaheen Mahira,S. Kapoor,Md Shadab Ali,Deepak Verma,Jay Singh,Sreelakshmi Badavenkatappa Gari,Prabhat Upadhyay,Yeva Meshkovska,C. Godugu,Sowjanya Thatikonda,Venkatesh Pooladanda

Published 2025 in Frontiers in Pharmacology

ABSTRACT

Cancer is a major threat to public health today, particularly due to the emergence of drug resistance and disease re-emergence post-traditional treatment. Regulatory T cells (Tregs) support cancer progression through their immunosuppressive mechanisms expressing co-inhibitory molecules like programmed cell death-1 (PD-1), cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), T cell immunoglobin-3 (TIM-3), and T-cell immunoglobin and ITIM domain (TIGIT), that suppress T-cell activation and allow tumor cells to grow uncontrollably. Emerging cancer immunotherapeutic strategies targeting these checkpoints inhibit tumor-immune escape and impede cancer progression. This review highlights the mechanistic effects of these drugs and enumerates various critical combinatorial strategies that can be utilized for effective cancer treatment.

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