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

Author:

Martin Timothy D.1ORCID,Patel Rupesh S.1ORCID,Cook Danielle R.23,Choi Mei Yuk1,Patil Ajinkya1ORCID,Liang Anthony C.1ORCID,Li Mamie Z.1ORCID,Haigis Kevin M.23,Elledge Stephen J.1ORCID

Affiliation:

1. Division of Genetics, Brigham and Women’s Hospital, Howard Hughes Medical Institute, Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.

2. Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.

3. Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USA.

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

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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