Epithelial memory of inflammation limits tissue damage while promoting pancreatic tumorigenesis

Author:

Del Poggetto Edoardo1ORCID,Ho I-Lin12ORCID,Balestrieri Chiara34ORCID,Yen Er-Yen12ORCID,Zhang Shaojun1ORCID,Citron Francesca1ORCID,Shah Rutvi12ORCID,Corti Denise1ORCID,Diaferia Giuseppe R.5ORCID,Li Chieh-Yuan12ORCID,Loponte Sara1ORCID,Carbone Federica1ORCID,Hayakawa Yoku6ORCID,Valenti Giovanni6,Jiang Shan1,Sapio Luigi1,Jiang Hong1,Dey Prasenjit7ORCID,Gao Sisi1ORCID,Deem Angela K.1,Rose-John Stefan8ORCID,Yao Wantong9ORCID,Ying Haoqiang10ORCID,Rhim Andrew D.11,Genovese Giannicola12,Heffernan Timothy P.13ORCID,Maitra Anirban14ORCID,Wang Timothy C.6ORCID,Wang Linghua1ORCID,Draetta Giulio F.1ORCID,Carugo Alessandro13ORCID,Natoli Gioacchino515,Viale Andrea1ORCID

Affiliation:

1. Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

2. MD Anderson UTHealth Graduate School of Biomedical Sciences, Houston, TX 77030, USA.

3. Experimental Hematology Unit, San Raffaele Research Hospital, Milan 20132, Italy.

4. Center for Omics Sciences, IRCCS San Raffaele Scientific Institute, Milan 20132, Italy.

5. Department of Experimental Oncology, European Institute of Oncology IRCCS, Milan 20139, Italy.

6. Department of Digestive and Liver Diseases, Columbia University Medical Center, New York, NY 10032, USA.

7. Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

8. Department of Biochemistry, Christian-Albrechts-Universität zu Kiel, Kiel 24098, Germany.

9. Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

10. Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

11. Department of Gastroenterology Hepatology and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

12. Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

13. TRACTION, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

14. Sheikh Ahmed Center for Pancreatic Cancer Research, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

15. Humanitas University, Pieve Emanuele, Milan 20089, Italy.

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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