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Review
. 2025 Jun 13:16:1602529.
doi: 10.3389/fphar.2025.1602529. eCollection 2025.

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

Neeharika Vatsavai #  1 , Sumeet Kaur Bhinder #  2 , Rahaman Shaik #  3 , Shaheen Mahira #  4 , Shruti Kapoor  5 , Md Shadab Ali  6 , Deepak Verma  7 , Jay Singh  8 , Sreelakshmi Badavenkatappa Gari  9 , Prabhat Upadhyay  10   11 , Yeva Meshkovska  12 , Chandraiah Godugu  13 , Sowjanya Thatikonda  12 , Venkatesh Pooladanda  10   11
Affiliations
Review

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

Neeharika Vatsavai et al. Front Pharmacol. .

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.

Keywords: CTLA-4; PD-1; cancer immunotherapy; immune checkpoints; regulatory T cells; tumor immune evasion.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.

Figures

FIGURE 1
FIGURE 1
Mechanisms of immune checkpoint inhibition in cancer immunotherapy. Different mechanisms of immune-checkpoint inhibition in cancer immunotherapy, emphasizing the regulation of T cell activation through interactions with cancer cells and dendritic cells. Pembrolizumab, Nivolumab, Cemiplimab (PD-1), and Atezolizumab, Avelumab, Durvalumab (PD-L1) block PD-1/PD-L1 Axis. Ipilimumab obstructs CTLA-4/B7 interaction. IMP3, Lerapamilimab, MK-4280 target emerging checkpoint pathways like LAG3. The figure contains modified images from Servier Medical Art, licensed under Creative Commons attribution 4.0 Unported License.
FIGURE 2
FIGURE 2
Organ-specific immune-related adverse events (irAEs) induced by immune checkpoint inhibitors in cancer therapy. irAEs Development. Immune-related Adverse Events (irAEs) can affect any organ system. Different immunotherapy drugs cause different irAEs in different organs. For example, endocrine toxicity (Nivolumab), dermatologic toxicity (Camrelizumab), hypothyroidism (Atezolizumab), and pneumonitis and hepatitis (Pembrolizumab). The occurrence of grade 3/4 irAEs is an indicator of discontinuing immunotherapy. The figure contains modified images from Servier Medical Art, licensed under Creative Commons attribution 4.0 Unported License.
FIGURE 3
FIGURE 3
integrative strategies to enhance cancer immunotherapy through immune system modulation. Various treatment strategies that leverage the immune system to enhance cancer immunotherapy. Either stand-alone or as a combination of multiple approaches, such as chemotherapy, radiotherapy, and cancer vaccines, the overarching objective is to enhance the therapeutic outcomes of cancer immunotherapy. The figure contains modified images from Servier Medical Art, licensed under Creative Commons attribution 4.0 Unported License.
See this image and copyright information in PMC

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