Kevin Barry, Ph.D.

 

ASSISTANT PROFESSOR, PUBLIC HEALTH SCIENCES DIVISION, FRED HUTCHINSON CANCER RESEARCH CENTER
AFFILIATE ASSISTANT PROFESSOR, IMMUNOLOGY

Dr. Barry completed his undergraduate studies at the University of Washington in 2007 and earned a PhD in Molecular and Cell Biology in Dr. Russell Vance’s laboratory at the University of California, Berkeley in 2015. He then completed his postdoctoral studies in Dr. Matthew Krummel’s laboratory at the University of California, San Francisco. In 2019 Dr. Barry joined the Translational Research Program within the Division of Public Health Sciences at the Fred Hutchinson Cancer Center as an Assistant Professor and in 2021 he joined the UW Department of Immunology as a Affiliate Assistant Professor.

RESEARCH

Immunotherapies, such as anti-PD-1 immunotherapy, aim to reactivate T cell responses to cancer. While anti-PD-1 immunotherapy provides long lasting protection to some patients, a large number of patients have no responses to this treatment. Thus, our lab is focused on understanding how to increase patient responses to current immunotherapies, as well as identifying components of the immune system that can be targeted to generate the next generation of immunotherapies. We are particularly interested in understanding how the innate immune system acts to regulate immune responses to cancer and could be harnessed in concert with anti-PD-1 immunotherapy to increase the number of patients being protected from these treatments.

It is well established that dendritic cells (DCs) are found in the tumor microenvironment and a subset of these cells, termed cDC1s, are required for T cell mediated anti-tumor responses. Our previous work has found that cDC1s correlate with increased survival and responses to anti-PD-1 immunotherapy in metastatic melanoma patients. We further discovered that cDC1s in the tumor make close contacts with natural killer (NK) cells and went on to show that NK cells correlate with better overall survival, responses to anti-PD-1 immunotherapy, and control cDC1 abundance in the tumor by producing the cytokine FLT3LG. Our previous findings suggest a model in which NK cell production of FLT3LG in the tumor microenvironment regulates cDC1 abundance, subsequent activation of T cell-dependent killing of tumor cells, and augments reactivation of the immune system by anti-PD-1 immunotherapy.

We hypothesize that targeting NK cells may lead to increased levels of protective cDC1s in the tumor, better tumor directed T cell-responses, and increased efficacy of current immunotherapies. Future research in the lab will focus on understanding the cellular and molecular mechanisms regulating NK cells and DCs in the tumor. We aim to identify key pathways that can be targeted to harness the NK-DC axis to shape anti-tumor immunity and responses to immunotherapy.

PUBLICATIONS

1. Barry KC, Hsu J, Broz ML, Cueto FJ, Binnewies M, Combes AJ, Nelson AE, Loo K, Kumar R, Rosenblum MD, Alvarado MD, Wolf DM, Bogunovic D, Bhardwaj N, Daud AI, Ha PK, Ryan WR, Pollack JL, Samad B, Asthana S, Chan V, Krummel MF. A natural killer-dendritic cell axis defines checkpoint therapy-responsive tumor microenvironments. Nat Med. 2018 Aug;24(8):1178-1191. doi: 10.1038/s41591-018-0085-8. Epub 2018 Jun 25. PMID: 29942093; PMCID: PMC6475503.
2. Bald T, Krummel MF, Smyth MJ, Barry KC. The NK cell-cancer cycle: advances and new challenges in NK cell-based immunotherapies. Nat Immunol. 2020 Aug;21(8):835-847. doi: 10.1038/s41590-020-0728-z. Epub 2020 Jul 20. PMID: 32690952; PMCID: PMC8406687.

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