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Targeting TNFR2 for cancer immunotherapy: recent advances and future directions
Linxue Li1, Ruiwei Ye1, Yingying Li1
1Shanghai Baoshan Luodian Hospital, School of Medicine, Shanghai University, Shanghai, 201908, China.
Abstract:
Cancer is the leading cause of death worldwide, accounting for nearly 10 million deaths every year. Immune checkpoint blockade approaches have changed the therapeutic landscape for many tumor types. However, current immune checkpoint inhibitors PD-1 or CTLA-4 are far from satisfactory, due to high immune-related adverse event incident (up to 60%) and the inefficiency in cases of "cold" tumor microenvironment. TNFR2, a novel hopeful tumor immune target, was initially proposed in 2017. It not only promotes tumor cell proliferation, but also correlates with the suppressive function of Treg cells, implicating in the development of an immunosuppressive tumor microenvironment. In preclinical studies, TNFR2 antibody therapy has demonstrated efficacy alone or a potential synergistic effect when combined with classical PD-1/ CTLA-4 antibodies. The focus of this review is on the characteristics, functions, and recent advancements in TNFR2 therapy, providing a new direction for the next generation of anti-tumor alternative therapy.
Insights
New research explores Tumor Necrosis Factor Receptor 2 (TNFR2) as a promising cancer immunotherapy target. TNFR2 antibody therapy shows potential to overcome limitations of current treatments like PD-1/CTLA-4 inhibitors, especially for difficult-to-treat tumors.
Area of Science:
- Oncology
- Immunology
- Cancer Research
Background:
- Cancer remains a leading global cause of death, with current immunotherapies like PD-1/CTLA-4 inhibitors having significant limitations.
- These limitations include high immune-related adverse events and ineffectiveness against "cold" tumors with immunosuppressive microenvironments.
Purpose of the Study:
- To review the characteristics, functions, and recent advancements in Tumor Necrosis Factor Receptor 2 (TNFR2) therapy.
- To highlight TNFR2 as a novel target for next-generation anti-cancer therapies.
Main Methods:
- Review of preclinical studies and existing literature on TNFR2.
- Analysis of TNFR2's role in tumor cell proliferation and Treg cell-mediated immunosuppression.
- Evaluation of TNFR2 antibody therapy efficacy, both as monotherapy and in combination with PD-1/CTLA-4 inhibitors.
Main Results:
- TNFR2 promotes tumor cell proliferation and is associated with suppressive Treg cell function, contributing to an immunosuppressive tumor microenvironment.
- Preclinical studies indicate TNFR2 antibody therapy demonstrates efficacy as a standalone treatment.
- TNFR2 antibody therapy shows potential synergistic effects when combined with PD-1/CTLA-4 inhibitors.
Conclusions:
- TNFR2 is a promising novel target for cancer immunotherapy.
- TNFR2 antibody therapy offers a potential alternative or complementary approach to current immunotherapies, addressing their limitations.
- Further research into TNFR2 therapy could lead to more effective cancer treatments, particularly for resistant tumors.
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