CSHL Menu
Douglas Fearon

Douglas Fearon

Professor
Cancer Center Member

M.D., Johns Hopkins University School of Medicine, 1968

dfearon@cshl.edu | 516-367-5420

Faculty Profile

I’m 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. Our underlying premise is that the tumor microenvironment is immune suppressive because cancer cells elicit responses characteristic of wound healing and tissue regeneration.  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.  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. 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. This immune suppression in murine and human pancreatic cancer has been interrupted by administering AMD3100, an inhibitor of the CXCL12 receptor, CXCR4, which leads to the rapid intra-tumoral accumulation of T cells. Since AMD3100 must be given by continuous intravenous administration, we are developing an anti-CXCR4 monoclonal antibody that would be administered every two weeks. Our next steps are to refine the necessary characteristics of this antibody.

See all Fearon news

Selected Publications

AMD3100/Plerixafor overcomes immune inhibition by the CXCL12-KRT19 coating on pancreatic and colorectal cancer cells.

26 Mar 2021 | British Journal of Cancer
Fearon, Douglas;  Janowitz, Tobias;  

CXCR4 inhibition in human pancreatic and colorectal cancers induces an integrated immune response

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;  

Cancer cell CCR2 orchestrates suppression of the adaptive immune response.

5 Oct 2020 | Journal of Experimental Medicine (JEM) | 217(10)
Fein, Miriam;  He, Xue-Yan;  Almeida, Ana;  Bružas, Emilis;  Pommier, Arnaud;  Yan, Ran;  Eberhardt, Anaïs;  Fearon, Douglas;  Van Aelst, Linda;  Wilkinson, John;  Dos Santos, Camila;  Egeblad, Mikala;  

CXCR4 inhibition in human pancreatic and colorectal cancers induces an integrated immune response

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;  

Autophagy Promotes Immune Evasion of Pancreatic Cancer by Degrading MHC-I

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

Signal peptide-independent secretion of keratin-19 by pancreatic cancer cells

20 Jan 2025 | bioRxiv
Moresco, Philip;  Kastan, Jonathan;  Yang, Jung-In;  Prabakar, Rishvanth;  Minicozzi, Francesca;  Adams, Dexter;  Cifani, Paolo;  Tuveson, David;  Fearon, Douglas;  

Intratumoral NKT cell accumulation promotes antitumor immunity in pancreatic cancer

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;  

Interaction between MED12 and ΔNp63 activates basal identity in pancreatic ductal adenocarcinoma

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;  

Plasma cells in human pancreatic ductal adenocarcinoma secrete antibodies to self-antigens

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;  

T cell-Mediated Development of Stromal Fibroblasts with an Immune-Enhancing Chemokine Profile

7 Jun 2023 | Cancer immunology research | :OF1-OF11
Yan, Ran;  Moresco, Philip;  Gegenhuber, Bruno;  Fearon, Douglas;  

See more publications