Douglas Fearon
Professor
Cancer Center Member
M.D., Johns Hopkins University School of Medicine, 1968
dfearon@cshl.edu | 516-367-5420
I鈥檓 studying how to harness the power of the immune system to fight cancer. Our underlying premise is that the microenvironment within a tumor suppresses the immune system. We have found a way to eliminate this suppression in the mouse model of pancreatic cancer, which has led to development of a drug for human pancreatic cancer that will enter phase 1 clinical trials in 2015.
The Fearon laboratory studies the interaction between cancer and the immune system.聽 Our underlying premise is that the tumor microenvironment is immune suppressive because cancer cells elicit responses characteristic of wound healing and tissue regeneration.聽 This approach has led to the finding that activated fibroblasts in the tumor stroma mediate immune suppression in several mouse models of cancer, including the autochthonous model of pancreatic ductal adenocarcinoma of the Tuveson lab.聽 Our understanding of the basis of immune suppression is evolving, but we know that it involves the production of the chemokine, CXCL12, by the fibroblastic stromal cells, binding of this CXCL12 by pancreatic cancer cells, and exclusion of T cells from the vicinity of the cancer cells.聽 T cell exclusion, which also occurs in several types of human adenocarcinomas, causes antagonists of T cell checkpoints to be ineffective, despite the presence of cancer-specific CD8+ T cells. 聽This immune suppression is interrupted by administering AMD3100, an inhibitor of CXCR4, the receptor for CXCL12, which leads to the rapid accumulation of T cells amongst cancer cells, thereby uncovering the efficacy of anti-PD-L1 and eliminating cancer cells.聽 Since human pancreatic cancer has certain immunological characteristics of the mouse model, a phase 1 clinical trial of AMD3100 in patients with pancreatic cancer will be initiated in 2015. 聽Some of our next steps are to determine the biological process that causes cancer cells to express non-mutated, shared antigens, and the means by which dormant metastases escape immune elimination.
Old chemo drug, new pancreatic cancer therapy?
August 26, 2024
Laboratoryscientists have found that folinic acid makes immunotherapy therapy more effective against pancreatic ductal adenocarcinoma in mice.
Can we crack this cancer鈥檚 immune response?
November 29, 2023
Laboratoryresearch brings scientists closer to understanding how pancreatic cancer interacts with our immune system and why immunotherapy hasn鈥檛 worked.
Laboratory2022 Ph.D.’s
May 1, 2022
The School of Biological Sciences awarded Ph.D. degrees to ten students this year. Here are some stories and memories from their time at 麻豆传媒社区.
Deactivating pancreatic cancer鈥檚 protective coat of arms
February 17, 2022
Find out how cancer cells shield themselves from the immune system using a coat of armor and confusing signals.
Pushing past pancreatic tumors鈥� defenses
February 16, 2022
A complex of proteins secreted by tumor cells can immobilize an important component of the immune system.
Giving the immune system a double boost against cancer
October 30, 2020
Immunotherapy enhances the body鈥檚 own defenses to kill cancer. A new regimen may increase the utility of these types of drugs.
Big bold dreamers
December 10, 2018
Dreamers drive discoveries. Laboratoryhonors its many scientists making big impacts in their respective fields.
Base Pairs Episode 15.5: Cellular hide and seek
June 15, 2018
Learn how William Coley's daughter founded the Cancer Research Institute, Professor Fearon on the immune system, and white blood cells on screen.
How pancreatic cancer spreads after surgery
May 17, 2018
Researchers have solved a mystery about how pancreatic cancer spreads
How deadly cancer spreads after surgery
May 17, 2018
Scientists have solved an important mystery about how pancreatic cancer spreads to the liver even after a successful surgery.
Selected Publications
26 Mar 2021 | British Journal of Cancer
Fearon, Douglas; Janowitz, Tobias;
17 Nov 2020 | Proceedings of the National Academy of Sciences of the United States of America | 117(46):28960-28970
Biasci, D; Smoragiewicz, M; Connell, C; Wang, Z; Gao, Y; Thaventhiran, J; Basu, B; Magiera, L; Johnson, T; Bax, L; Gopinathan, A; Isherwood, C; Gallagher, F; Pawula, M; Hudecova, I; Gale, D; Rosenfeld, N; Barmpounakis, P; Popa, E; Brais, R; Godfrey, E; Mir, F; Richards, F; Fearon, D; Janowitz, T; Jodrell, D;
5 Oct 2020 | Journal of Experimental Medicine (JEM) | 217(10)
Fein, Miriam; He, Xue-Yan; Almeida, Ana; Bru啪as, Emilis; Pommier, Arnaud; Yan, Ran; Eberhardt, Anaïs; Fearon, Douglas; Van Aelst, Linda; Wilkinson, John; Dos Santos, Camila; Egeblad, Mikala;
10 Jul 2020 | bioRxiv
Biasci, D; Smoragiewicz, M; Connell, C; Wang, Z; Gao, Y; Thaventhiran, J; Basu, B; Magiera, L; Johnson, I; Bax, L; Gopinathan, A; Isherwood, C; Gallagher, F; Pawula, M; Hudecova, I; Gale, D; Rosenfeld, N; Barmpounakis, P; Popa, E; Brais, R; Godfrey, E; Mir, F; Richards, F; Fearon, D; Janowitz, T; Jodrell, D;
May 2020 | Nature | 581(7806):100-105
Yamamoto, K; Venida, A; Yano, J; Biancur, D; Kakiuchi, M; Gupta, S; Sohn, A; Mukhopadhyay, S; Lin, E; Parker, S; Banh, R; Paulo, J; Wen, K; Debnath, J; Kim, G; Mancias, J; Fearon, D; Perera, R; Kimmelman, A;
All Publications
16 Jul 2024 | Proceedings of the National Academy of Sciences of the United States of America | 121(29):e2403917121
Li, Jiayun; Moresco, Philip; Fearon, Douglas;
17 Jun 2024 | Nature Genetics
Maia-Silva, Diogo; Cunniff, Patrick; Schier, Allison; Skopelitis, Damianos; Trousdell, Marygrace; Moresco, Philip; Gao, Yuan; Kechejian, Vahag; He, Xue-Yan; Sahin, Yunus; Wan, Ledong; Alpsoy, Aktan; Liverpool, Jynelle; Krainer, Adrian; Egeblad, Mikala; Spector, David; Fearon, Douglas; Dos Santos, Camila; Taatjes, Dylan; Vakoc, Christopher;
26 Sep 2023 | JCI insight | :e172449
Yao, Min; Preall, Jonathan; Yeh, Johannes; Pappin, Darryl; Cifani, Paolo; Zhao, Yixin; Shen, Sophia; Moresco, Philip; He, Brian; Patel, Hardik; Habowski, Amber; King, Daniel; Raphael, Kara; Rishi, Arvind; Sejpal, Divyesh; Weiss, Matthew; Tuveson, David; Fearon, Douglas;
7 Jun 2023 | Cancer immunology research | :OF1-OF11
Yan, Ran; Moresco, Philip; Gegenhuber, Bruno; Fearon, Douglas;
22 May 2023 | Cancer immunology research | 11(8):1044-1054
Yan, Ran; Moresco, Philip; Gegenhuber, Bruno; Fearon, Douglas;