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The exploitation of enzyme-based cancer immunotherapy

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Abstract

Cancer immunotherapy utilizes the immune system and its wide-ranging components to deliver anti-tumor responses. In immune escape mechanisms, tumor microenvironment-associated soluble factors and cell surface-bound molecules are mainly accountable for the dysfunctional activity of tumor-specific CD8+ T cells, natural killer (NK) cells, tumor associated macrophages (TAMs) and stromal cells. The myeloid-derived suppressor cells (MDSCs) and Foxp3+ regulatory T cells (Tregs), are also key tumor-promoting immune cells. These potent immunosuppressive networks avert tumor rejection at various stages, affecting immunotherapies' outcomes. Numerous clinical trials have elucidated that disruption of immunosuppression could be achieved via checkpoint inhibitors. Another approach utilizes enzymes that can restore the body’s potential to counter cancer by triggering the immune system inhibited by the tumor microenvironment. These immunotherapeutic enzymes can catalyze an immunostimulatory signal and modulate the tumor microenvironment via effector molecules. Herein, we have discussed the immuno-metabolic roles of various enzymes like ATP-dephosphorylating ectoenzymes, inducible Nitric Oxide Synthase, phenylamine, tryptophan, and arginine catabolizing enzymes in cancer immunotherapy. Understanding the detailed molecular mechanisms of the enzymes involved in modulating the tumor microenvironment may help find new opportunities for cancer therapeutics.

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Acknowledgements

Authors acknowledge the support from Maharishi Markandeshwar (Deemed to be University), Mullana, Ambala, Haryana, India.

Funding

The authors are grateful to Maharishi Markandeshwar (Deemed to be University) for providing financial support for writing this review article.

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Authors and Affiliations

  1. Central Research Cell, MM Institute of Medical Sciences and Research, Maharishi Markandeshwar (Deemed to Be University), Mullana, Ambala, 133207, Haryana, India

    Gourav Chandan, Sasanka Chakrabarti, Amit Mittal & Reena V. Saini

  2. Department of Biotechnology, MMEC, Maharishi Markandeshwar (Deemed to Be University), Mullana, Ambala, 133207, Haryana, India

    Adesh K. Saini, Anil Kumar Sharma & Reena V. Saini

  3. Department of Chemistry, Indian Institute of Technology, Roorkee, Uttarakhand, India

    Reena Kumari

  4. Department of Radiology, MM Institute of Medical Sciences & Research, Maharishi Markandeshwar (Deemed to be University), Mullana, Ambala, 133207, Haryana, India

    Amit Mittal

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  1. Gourav Chandan
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Contributions

Study concept and design: RVS and AKS. Data acquisition: GC, RK, RVS, and AKS. Analysis and interpretation of data: RVS, AKS, and AKS. Drafting the manuscript: GC and RK. Critical revision of the manuscript: SC, AM, and AKS. Study supervision: RVS. All authors have read and approved the final manuscript.

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Chandan, G., Saini, A.K., Kumari, R. et al. The exploitation of enzyme-based cancer immunotherapy. Human Cell 36, 98–120 (2023). https://doi.org/10.1007/s13577-022-00821-2

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