Chronic Viral Mimicry Induction following p53 Loss Promotes Immune Evasion

Charles A Ishak; Sajid A Marhon; Naïri Tchrakian; Anjelica Hodgson; Helen Loo Yau; Isabela M Gonzaga; Melanie Peralta; Ilinca M Lungu; Stephanie Gomez; Sheng-Ben Liang; Shu Yi Shen; Raymond Chen; Jocelyn Chen; Biji Chatterjee; Kevin N Wanniarachchi; Junwoo Lee; Nicholas Zehrbach; Amir Hosseini; Parinaz Mehdipour; Siyu Sun; Alexander Solovyov; Ilias Ettayebi; Kyle E Francis; Aobo He; Taiyi Wu; Shengrui Feng; Tiago da Silva Medina; Felipe Campos de Almeida; Jane Bayani; Jason Li; Spencer MacDonald; Yadong Wang; Sarah S Garcia; Elisa Arthofer; Noor Diab; Aneil Srivastava; Paul Tran Austin; Peter J B Sabatini; Benjamin D Greenbaum; Catherine A O'Brien; Trevor G Shepherd; Ming Sound Tsao; Katherine B Chiappinelli; Amit M Oza; Blaise A Clarke; Robert Rottapel; Stephanie Lheureux; Daniel D De Carvalho

doi:10.1158/2159-8290.CD-24-0094

Chronic Viral Mimicry Induction following p53 Loss Promotes Immune Evasion

Cancer Discov. 2025 Apr 2;15(4):793-817. doi: 10.1158/2159-8290.CD-24-0094.

Authors

Charles A Ishak^#^{1

2}, Sajid A Marhon^#¹, Naïri Tchrakian^#¹, Anjelica Hodgson^#¹, Helen Loo Yau^#³, Isabela M Gonzaga¹, Melanie Peralta¹, Ilinca M Lungu⁴, Stephanie Gomez⁵, Sheng-Ben Liang⁶, Shu Yi Shen¹, Raymond Chen³, Jocelyn Chen³, Biji Chatterjee^{2

7}, Kevin N Wanniarachchi², Junwoo Lee², Nicholas Zehrbach², Amir Hosseini^{1

8}, Parinaz Mehdipour^{1

8}, Siyu Sun⁹, Alexander Solovyov⁹, Ilias Ettayebi³, Kyle E Francis¹, Aobo He³, Taiyi Wu³, Shengrui Feng³, Tiago da Silva Medina¹, Felipe Campos de Almeida¹, Jane Bayani⁴, Jason Li⁴, Spencer MacDonald¹, Yadong Wang¹, Sarah S Garcia¹, Elisa Arthofer⁵, Noor Diab⁵, Aneil Srivastava⁵, Paul Tran Austin⁵, Peter J B Sabatini¹, Benjamin D Greenbaum⁹, Catherine A O'Brien¹, Trevor G Shepherd¹⁰, Ming Sound Tsao^{1

3}, Katherine B Chiappinelli⁵, Amit M Oza¹, Blaise A Clarke¹, Robert Rottapel^{1

3}, Stephanie Lheureux¹, Daniel D De Carvalho^{1

3}

Affiliations

¹ Princess Margaret Cancer Centre, University Health Network, Toronto, Canada.
² Department of Epigenetics and Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Houston, Texas.
³ Department of Medical Biophysics, University of Toronto, Toronto, Canada.
⁴ Diagnostic Development Program, Ontario Institute of Cancer Research, Toronto, Canada.
⁵ Department of Microbiology, Immunology and Tropical Medicine, The George Washington University Cancer Center, The George Washington University School of Medicine and Health Sciences, Washington, District of Columbia.
⁶ Princess Margaret Cancer Biobank, University Health Network, Toronto, Canada.
⁷ Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas.
⁸ Ludwig Institute for Cancer Research, University of Oxford, Oxford, United Kingdom.
⁹ Department of Epidemiology and Biostatistics, Halvorsen Center for Computational Oncology, Memorial Sloan Kettering Cancer Center, New York, New York.
¹⁰ Department of Obstetrics and Gynaecology, Western University, London, Canada.

^# Contributed equally.

Abstract

Our landmark discovery of viral mimicry characterized repetitive elements as immunogenic stimuli that cull cancer cells. If expressed repetitive elements cull cancer cells, why does every human cancer express repetitive elements? Our report offers an exciting advancement toward understanding this paradox and how to exploit this mechanism for cancer interception. See related commentary by Murayama and Cañadas, p. 670.

MeSH terms

Humans
Immune Evasion*
Molecular Mimicry*
Neoplasms* / genetics
Neoplasms* / immunology
Tumor Suppressor Protein p53* / genetics
Tumor Suppressor Protein p53* / metabolism

Substances

Tumor Suppressor Protein p53

Abstract

MeSH terms

Substances

Grants and funding