The adaptive immune system is a major driver of selection for tumor suppressor gene inactivation

Timothy D. Martin(Howard Hughes Medical Institute), Rupesh S. Patel(Howard Hughes Medical Institute), Danielle Cook(Brigham and Women's Hospital), Mei Yuk Choi(Howard Hughes Medical Institute), Ajinkya Patil(Howard Hughes Medical Institute), Anthony C. Liang(Howard Hughes Medical Institute), Mamie Z. Li(Howard Hughes Medical Institute), Kevin M. Haigis(Brigham and Women's Hospital), Stephen J. Elledge(Howard Hughes Medical Institute)
Science
September 16, 2021
Cited by 157

Abstract

Defining tumor cell immune evasion Mouse models used to study cancer often lack a full immune system, allowing implantation of human tumors into the mice. By contrast, naturally evolving tumors must contend with a fully functional immune system and its destruction of some of the cells (see the Perspective by Ho and Wood). Two groups now report studies on mouse models with a fully intact immune system. Martin et al . started with preexisting murine tumor cell lines and examined their continued evolution in vivo, whereas Del Poggetto et al . examined the development of new pancreatic tumors in the context of inflammation, as is often seen in human patients. In each study, the authors found that the immune system exerted a selective pressure on cells that would give rise to tumors, promoting the survival of those that had lost expression of tumor suppressor genes or activated a specific oncogene. The findings suggest a major role for the immune system in driving tumor evolution across multiple types of cancer. —YN


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