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Recent Advances of RNA m6A Modifications in Cancer Immunoediting and Immunotherapy

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Epigenetics in Oncology

Part of the book series: Cancer Treatment and Research ((CTAR,volume 190))

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Abstract

Cancer immunotherapy, which modulates immune responses against tumors using immune-checkpoint inhibitors or adoptive cell transfer, has emerged as a novel and promising therapy for tumors. However, only a minority of patients demonstrate durable responses, while the majority of patients are resistant to immunotherapy. The immune system can paradoxically constrain and promote tumor development and progression. This process is referred to as cancer immunoediting. The mechanisms of resistance to immunotherapy seem to be that cancer cells undergo immunoediting to evade recognition and elimination by the immune system. RNA modifications, specifically N6-methyladenosine (m6A) methylation, have emerged as a key regulator of various post-transcriptional gene regulatory processes, such as RNA export, splicing, stability, and degradation, which play unappreciated roles in various physiological and pathological processes, including immune system development and cancer pathogenesis. Therefore, a deeper understanding of the mechanisms by which RNA modifications impact the cancer immunoediting process can provide insight into the mechanisms of resistance to immunotherapies and the strategies that can be used to overcome such resistance. In this chapter, we briefly introduce the background of cancer immunoediting and immunotherapy. We also review and discuss the roles and mechanisms of RNA m6A modifications in fine-tuning the innate and adaptive immune responses, as well as in regulating tumor escape from immunosurveillance. Finally, we summarize the current strategies targeting m6A regulators for cancer immunotherapy.

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Authors and Affiliations

  1. Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Los Angeles, CA, 91010, USA

    Shoubao Ma, Tasha Barr & Jianhua Yu

  2. Hematologic Malignancies and Stem Cell Transplantation Institute, City of Hope National Medical Center, Los Angeles, CA, 91010, USA

    Shoubao Ma, Tasha Barr & Jianhua Yu

  3. Department of Immuno-Oncology, Beckman Research Institute, City of Hope, Los Angeles, CA, 91010, USA

    Jianhua Yu

  4. Comprehensive Cancer Center, City of Hope, Los Angeles, CA, 91010, USA

    Jianhua Yu

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  1. Shoubao Ma
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  2. Tasha Barr
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  3. Jianhua Yu
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Correspondence to Jianhua Yu .

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  1. Department of Systems Biology, City of Hope National Medical Center, Duarte, CA, USA

    Jianjun Chen

  2. Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Chapel Hill, NC, USA

    G. Greg Wang

  3. Stem Cell Center, Yale University School of Medicine, New Haven, CT, USA

    Jun Lu

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Ma, S., Barr, T., Yu, J. (2023). Recent Advances of RNA m6A Modifications in Cancer Immunoediting and Immunotherapy. In: Chen, J., Wang, G.G., Lu, J. (eds) Epigenetics in Oncology . Cancer Treatment and Research, vol 190. Springer, Cham. https://doi.org/10.1007/978-3-031-45654-1_3

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