The goal of the TIME Lab is to develop a precise understanding of the nature of the adaptive immune response to solid tumors, in order to develop effective immunotherapies. While much of our work focuses on pancreatic and colorectal carcinoma, we are particularly interested in shedding light on aspects of tumor biology that reach across many tumor types. Our central goal is to address is how the immunosuppressive microenvironment created by solid tumors can be altered to enable reactivation of endogenous T cell responses. In concert with this work, we are also finding that adoptively transferred T cells (e.g. CAR-T cells) are subject to similar mechanisms of immunosuppression in the TIME.

We are fortunate to have multiple world-class collaborators:

Courtney Crane, PhD, Associate Professor, UW Department of Neurosurgery, Principal Investigator, Ben Towne Center for Childhood Cancer Research

Ian N. Crispe, MBBS, PhD, Professor, UW Department of Pathology

Steven C. Katz, Associate Professor, Boston University Department of Surgery; Director, Surgical Immunotherapy, Roger Williams Medical Center, Providence, RI

Teresa S. Kim, MD, Assistant Professor, UW Department of Surgery; co-PI UW TIME Lab

George Miller, MD, Professor, Vice-Chair of Research, New York University Department of Surgery

Paul T. Nghiem, MD, PhD, Professor UW Dermatology/Medicine; George F. Odland Chair in Dermatology, Head of UW Dermatology

Robert H. Pierce, MD, Member, Fred Hutchinson Cancer Research Center, Program in Immunology, Clinical Research Division; Scientific Director, Immunopathology Lab

Seth M. Pollack, MD, Assistant Member, Fred Hutchinson Cancer Research Center, Program in Immunology, Clinical Research Division

Harlan Robins, PhD, Member, Fred Hutchinson Cancer Research Center, Program Head, Computational Biology

Eric Seibel, MS, PhD, Research Professor, UW Department of Mechanical Engineering

Qiang Tian, MD, PhD, Senior Research Scientist, Institute for Systems Biology

Joshua Veatch, MD, PhD, Acting Instructor, UW Department of Medicine, Division of Medical Oncology

Raymond S. Yeung, MD, Professor, UW Department of Surgery; Director, Northwest Liver Research Program

United States Army Medical Research Acquisition Activity
Tumor Slice Culture: A new avatar in personalized oncology 

Ipsen Biopharmaceuticals
A Phase II Trial of Lanreotide for the Prevention of Postoperative Pancreatic Fistula

Cancer Research Institute
Fibrolamellar Cancer Foundation Fellowship - Kevin Sullivan (Fellow)
T cell immunotherapy in fibrolamellar cancer

Merck Investigator Studies Program
Defining and overcoming mechanisms of resistance to pembrolizumab in pancreatic ductal adenocarcinoma and microsatellite-stable colorectal cancer

Seattle Translational Tumor Research (STTR)
Defining the response of tumor slice cultures to chemotherapy and immunotherapy 

Brotman Baty Institute for Precision Medicine
Identification and characterization of tumor-specific T cells in pancreatic ductal adenocarcinoma 

Brotman Baty Institute for Precision Medicine
Defining the single cell transcriptomic response to immunotherapy using tumor slice cultures

1. Jiang X, Seo YD, Sullivan KM, Pillarisetty VG. Establishment of Slice Cultures as a Tool to Study the Cancer Immune Microenvironment. Methods Mol Biol. 2019;1884:283-295. doi: 10.1007/978-1-4939-8885-3_20.
2. Sullivan KM, Kenerson HL, Pillarisetty VG, Riehle KJ, Yeung RS. Precision oncology in liver cancer. Ann Transl Med. 2018 Jul;6(14):285. doi: 10.21037/atm.2018.06.14. Review.
3. Jiang X, Seo YD, Chang JH, Coveler A, Nigieh E, Pan S, Jalikis F, Yeung RS, Crispe IN, Pillarisetty VG. Long-lived pancreatic ductal adenocarcinoma slice cultures enable precise study of the immune microenvironment. 2017 May 25;6(7):e1333210. doi: 10.1080/2162402X.2017.1333210. eCollection 2017. PMID: 28811976
4. Chen R, Lai LA, Sullivan Y, Wong M, Wang L, Riddell J, Jung L, Pillarisetty VG, Brentnall TA, Pan S. Disrupting glutamine metabolic pathways to sensitize gemcitabine-resistant pancreatic cancer. Sci Rep. 2017 Aug 11;7(1):7950. doi: 10.1038/s41598-017-08436-6. PMID 28801576
5. Pollack SM, He Q, Yearley JH, Emerson R, Vignali M, Zhang Y, Redman MW, Baker KK, Cooper S, Donahue B, Loggers ET, Cranmer LD, Spraker MB, Seo YD, Pillarisetty VG, Ricciotti RW, Hoch BL, McClanahan TK, Murphy E, Blumenschein WM, Townson SM, Benzeno S, Riddell SR, Jones RL. T-cell infiltration and clonality correlate with programmed cell death protein 1 and programmed death-ligand 1 expression in patients with soft tissue sarcomas. 2017 May 2. doi: 10.1002/cncr.30726. [Epub ahead of print] PMID 28463396
6. Smith T, Moffett H, Stephan S, Dumigan A, Jiang X, Pillarisetty V, Stephan M. Biopolymers co-delivering T cells and STING agonists can eliminate heterogeneous tumors. J Clin Invest. 2017 Apr 24. pii: 87624. doi: 10.1172/JCI87624. [Epub ahead of print] PMID 28436934
7. Chang JH, Jiang Y, Pillarisetty VG. Role of immune cells in pancreatic cancer from bench to clinical application: An updated review. Medicine (Baltimore). 2016 Dec;95(49):e5541.
8. Seo YD, Pillarisetty VG. T-cell programming in pancreatic adenocarcinoma: a review. Cancer Gene Therapy. 2017 Mar;24(3):106-113. doi: 10.1038/cgt.2016.66. Epub 2016 Dec 2. Review.
9. Daley D, Tomkötter L, Zambirinis CP, Alothman S, Alqunaibit D, Werba G, Jang J, Barilla R, Narayanan R, Avanzi N, Tippens D, Mohan N, Savithta, Torres-Hernandez A, Newman E, Hajdu C, Pillarisetty VG, Dustin ML, Bar-Sagi D, Miller G. γδ T Cells Support Pancreatic Oncogenesis by Inducing αβ T Cell Exhaustion. Cell. 2016 Aug 25. pii: S0092-8674(16)30996-5. doi: 10.1016/j.cell.2016.07.046.
10. Pillarisetty VG. The pancreatic cancer microenvironment: an immunologic battleground. OncoImmunology. 2014 Aug 3;3(8):e950171. eCollection 2014.
11. Pollack SM, Jones RL, Farrar EA, Lai IP, Lee SM, Cao J, Pillarisetty VG, Hoch BL, Gullett A, Conrad EU, Eary JF, Shibuya KC, Warren EH, Carstens JN, Heimfeld S, Riddell SR, Yee C. Tetramer Guided, Cell Sorter Assisted Production of Clinical Grade Autologous NY-ESO-1 Specific CD8+ T Cells. Journal for ImmunoTherapy of Cancer. 2014 Oct 14;2(1):36. doi: 10.1186/s40425-014-0036-y. eCollection 2014
12. Jiang Y, Du Z, Yang F, Di T, Li J, Zhou Z, Pillarisetty VG, Fu D. FOXP3⁺ Lymphocyte Density in Pancreatic Cancer Correlates with Lymph Node Metastasis. PLoS ONE 9(9): e106741. doi:10.1371/journal.pone.0106741
13. Khan H, Pillarisetty VG, Katz SC. The Prognostic Value of Liver Tumor T Cell Infiltrates. Journal of Surgical Research2014 Sep;191(1):189-195. doi: 10.1016/j.jss.2014.06.001.
14. Shibuya KC, Goel VK, Xiong W, Sham JG, Pollack SM, Leahy AM, Whiting SH, Yeh MM, Yee C, Riddell SR, Pillarisetty VG. Pancreatic ductal adenocarcinoma contains an effector and regulatory immune cell infiltrate that is altered by multimodal neoadjuvant treatment. PLOS ONE 2014 May 2.
15. Katz SC, Bamboat ZM, Maker AV, Shia J, Pillarisetty VG, Yopp AC, Hedvat CV, Gonen M, Jarnagin WR, Fong Y, D'Angelica MI, DeMatteo RP. Regulatory T cell infiltration predicts outcome following resection of colorectal cancer liver metastases. Annals of Surgical Oncology 2013 Mar;20(3):946-55.
16. Katz SC, Donkor C, Glasgow K, Pillarisetty VG, Gönen M, Espat NJ, Klimstra DS, D'Angelica MI, Allen PJ, Jarnagin W, Dematteo RP, Brennan MF, Tang LH. T cell infiltrate and outcome following resection of intermediate-grade primary neuroendocrine tumours and liver metastases. HPB (Oxford). 2010 Dec;12(10):674-83.
17. Katz SC, Pillarisetty V, Bamboat ZM, Shia J, Hedvat C, Gonen M, Jarnagin W, Fong Y, Blumgart L, D'Angelica M, Dematteo RP. T Cell Infiltrate Predicts Long-Term Survival Following Resection of Colorectal Cancer Liver Metastases. Annals of Surgical Oncology 2009 Sep;16(9):2524-30.
18. Bleier JI, Katz SC, Chaudhry UI, Pillarisetty VG, Kingham PT, Shah AB, Raab JR, DeMatteo RP. Biliary obstruction selectively expands and activates liver myeloid dendritic cells. The Journal of Immunology 2006 June 15; 176(12): 7189-7195.
19. Katz SC, Pillarisetty VG, Bleier JI, Kingham TP, Chaudhry UI, Shah AB, DeMatteo RP. Conventional liver CD4 T cells are functionally distinct and suppressed by environmental factors. Hepatology 2005 August; 42(2): 293-300.
20. Pillarisetty VG, Katz SC, Bleier JI, Shah AB, DeMatteo RP. Natural killer dendritic cells have both antigen presenting and lytic function and in response to CpG produce IFN-γ via autocrine IL-12. The Journal of Immunology 2005 March 1; 174(5): 2612-2618.
21. Katz SC, Pillarisetty VG, Bleier JI, Shah AB, DeMatteo RP. Liver sinusoidal endothelial cells are insufficient to activate T cells. The Journal of Immunology 2004 July 1; 172(13): 230-235.
22. Bleier JI, Pillarisetty VG, Shah AB, DeMatteo RP. Increased and long-term generation of dendritic cells from with reduced function from IL-6-deficient bone marrow. The Journal of Immunology 2004 June 15; 172(12): 7408-7416.
23. Miller G, Bleier JI, Antonescu C, Pillarisetty VG, Shah AB, Lahrs SJ, DeMatteo RP. Natural killer cell depletion confounds the anti-tumor mechanism of endogenous IL-12 overexpression. International Journal of Cancer 2004 June 20: 110:395-402.
24. Pillarisetty VG, Shah AB, Miller G, Bleier JI, DeMatteo RP. Liver dendritic cells are less immunogenic than spleen dendritic cells because of differences in subtype composition. The Journal of Immunology 2004 Jan 15; 172(2): 1009-1017.
25. Pillarisetty VG, Miller G, Shah AB, DeMatteo RP. GM-CSF expands dendritic cells and their progenitors in mouse liver. Hepatology 2003 Mar; 37(3): 641-652.

Dr. Venu Pillarisetty's UW Medicine Biography >>