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Viral and cellular oncogenes promote immune evasion

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Abstract

Thirteen percent of cancers worldwide are associated with viral infections. While many human oncogenic viruses are widely endemic, very few infected individuals develop cancer. This raises the question why oncogenic viruses encode viral oncogenes if they can replicate and spread between human hosts without causing cancer. Interestingly, viral infection triggers innate immune signaling pathways that in turn activate tumor suppressors such as p53, suggesting that tumor suppressors may have evolved not primarily to prevent cancer, but to thwart viral infection. Here, we summarize and compare several major immune evasion strategies used by viral and non-viral cancers, with a focus on oncogenes that play dual roles in promoting tumorigenicity and immune evasion. By highlighting important and illustrative examples of how oncogenic viruses evade the immune system, we aim to shed light on how non-viral cancers avoid immune detection. Further study and understanding of how viral and non-viral oncogenes impact immune function could lead to improved strategies to combine molecular therapies targeting oncoproteins in combination with immunomodulators.

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Fig. 1: Viral and cellular oncoproteins inhibit the cGAS/STING pathway.
Fig. 2: Viral and cellular oncoproteins modulate cytokine production to change the immune landscape.
Fig. 3: Viral and cellular oncoproteins inhibit MHC class I and antigen processing/presentation.
Fig. 4: Viral and cellular oncoproteins upregulate checkpoint molecules such as PD-L1.

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Acknowledgements

This work was supported by funding from the V Foundation, P30DK058404, 50CA098131, and the Serodino Adventure Allee Fund.

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Authors and Affiliations

  1. Program in Cancer Biology, Vanderbilt University, Nashville, TN, USA

    Jessica J. Roetman & Mary Philip

  2. Department of Biochemistry and Chemical Biology, Vanderbilt University, Nashville, TN, USA

    Minna K. I. Apostolova

  3. Department of Medicine, Division of Hematology and Oncology, Vanderbilt University Medical Center, Nashville, TN, USA

    Mary Philip

Authors
  1. Jessica J. Roetman
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  2. Minna K. I. Apostolova
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  3. Mary Philip
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Contributions

JJR wrote and edited the manuscript and prepared the figures and table. MKIA contributed to the section on checkpoint molecules. MP wrote and edited the manuscript. All authors approved the final version.

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Correspondence to Mary Philip.

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Roetman, J.J., Apostolova, M.K.I. & Philip, M. Viral and cellular oncogenes promote immune evasion. Oncogene 41, 921–929 (2022). https://doi.org/10.1038/s41388-021-02145-1

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