Headshot of Tim Greten

Tim F. Greten, M.D.

  • Center for Cancer Research
  • National Cancer Institute


Dr. Greten is a physician-scientist who uses his medical expertise in Gastroenterology, Hepatology and Medical Oncology along with his research expertise in tumor immunology to develop novel treatments for patients with cancer. He heads a research team to study the tumor microenvironment in the liver in the context of Hepatocellular Carcinoma, Cholangiocarcinoma, and liver metastasis and studies how exogenous factors such as diet and the gut microbiome may affect immune responses in the liver. He also directs the GI Medical Oncology clinical team, that conducts clinical trials in patients with GI cancers. He and his team cover the entire research spectrum from basic tumor immunology and use of complex murine cancer models to the development and evaluation of new immunotherapies (including CAR T cells) for patients with gastrointestinal cancers. He conducts investigator-initiated first-in-human trials, phase I and II trials and has been one of the first investigators to test immune checkpoint inhibitors in patients with Hepatocellular carcinoma and Cholangiocarcinoma either alone or in combination with locoregional therapies.

Areas of Expertise

Tumor Immunology
Gastrointestinal Cancers
Complex Murine Cancer Models

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Dr. Greten has been studying immunotherapy of GI cancers for more than 20 years. After a post-doctoral fellowship at Johns Hopkins, where he developed MHC-IgG fusion proteins to detect tumor-specific T cells in patients with cancer and studied the effect of tumor cell death on tumor specific immune responses, he decided to focus on primary liver cancer and the specific tumor microenvironment in the liver.

Dr. Greten has been a pioneer in studying tumor-specific immune responses in patients with hepatocellular carcinoma (HCC). Very early on he made the unexpected observation that patients with HCC mount spontaneous tumor-specific immune responses, which led to the question of why tumors would progress if tumor-specific T cells were present. He described in his early studies an accumulation of suppressive regulatory T cells and was one of the pioneers to study another cell type with immune suppressor function, CD14+ HLA-DRlo myeloid derived suppressor cells. Based on these findings, he conducted small proof of concept clinical trials targeting regulatory T cells and a peptide vaccine approach to enhance anti-tumor immunity in HCC. Based on the clinical observation that non-alcoholic fatty liver disease (NAFLD) is a risk factor to develop HCC; Dr. Greten developed a mouse model, which helped him, and his group explain the cellular and metabolic mechanism ultimately leading to impaired immune responses in NAFLD. This work led to multiple high impact publications in Nature, Gastroenterology, Journal of Hepatology and other scientific journals. Based on the observation that different diets can change immune responses in the liver through immediate interactions with fatty acids accumulating in the liver in non-alcoholic fatty liver disease, Dr. Greten decided to extend those studies and explore whether the gut microbiome may also affect immune responses in the liver because of the specific anatomical location of the liver with the immediate connection to the gut through the portal vein. His group demonstrated that commensal bacteria control bile acid metabolism, which indeed control NKT cells in the liver (Science, 2018). His current research portfolio includes basic research studies on the gut microbiome, NAFLD and how they affect anti-tumor immunity in the liver. His research combines studies on human samples, complex murine models as well as early investigator-initiated trials.

Dr. Greten has been highly successful both in his clinical and laboratory research with publications in leading journals including Nature, Science, Cancer Cell, Cancer Discovery etc. He is a pioneer for the field of immunotherapy of liver cancers, which now have become standard of care. Dr. Greten has mentored many students and fellows at different levels of their career. He is internationally recognized as a leader in the field of immunotherapy of liver cancers and in 2023 he has been recognized as the most published author in the field of hepatocellular carcinoma immunotherapy worldwide.

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Selected Key Publications

Gut microbiome-mediated bile acid metabolism regulates liver cancer via NKT cells

Ma C, Han M, Heinrich B, Fu Q, Zhang Q, Sandhu M, Agdashian D, Terabe M, Berzofsky JA, Fako V, Ritz T, Longerich T, Theriot CM, McCulloch JA, Roy S, Yuan W, Thovarai V, Sen SK, Ruchirawat M, Korangy F, Wang XW, Trinchieri G, Greten TF.
Science. 360(6391): 2018. [ Journal Article ]

NAFLD causes selective CD4(+) T lymphocyte loss and promotes hepatocarcinogenesis

Ma C, Kesarwala AH, Eggert T, Medina-Echeverz J, Kleiner DE, Jin P, Stroncek DF, Terabe M, Kapoor V, ElGindi M, Han M, Thornton AM, Zhang H, Egger M, Luo J, Felsher DW, McVicar DW, Weber A, Heikenwalder M, Greten TF.
Nature. 531(7593): 253-7, 2016. [ Journal Article ]

Tumor-associated macrophages trigger MAIT cell dysfunction at the HCC invasive margin

Ruf B, Bruhns M, Babaei S, Kedei N, Ma L, Revsine M, Benmebarek M-R, Ma C, Heinrich B, Subramanyam V, Qi J, Wabitsch S, Green BL, Bauer KC, Myojin Y, Greten LT, McCallen JD, Huang P, Trehan R, Wang X, Nur A, Murphy Soika DQ, Pouzolles M, Evans CN, Chari R, Kleiner DE, Telford W, Dadkhah K, Ruchinskas A, Stovroff MK, Kang J, Oza K, Ruchirawat M, Kroemer A, Wang XW, Claassen M, Korangy F, Greten TF
Cell. 186: 3686-3705, 2023. [ Journal Article ]

Tremelimumab in Combination with Ablation in Patients with Advanced Hepatocellular Carcinoma

Duffy AG, Ulahannan SV, Makorova-Rusher O, Rahma O, Wedemeyer H, Pratt D, Davis JL, Hughes MS, Heller T, ElGindi M, Uppala A, Korangy F, Kleiner DE, Figg WD, Venzon D, Steinberg SM, Venkatesan AM, Krishnasamy V, Abi-Jaoudeh N, Levy E, Wood BJ, Greten TF.
Journal of Hepatology. 66(3): 545-551, 2017. [ Journal Article ]

Platelets control liver tumor growth through P2Y12-dependent CD40L release in NAFLD

Ma C, Fu Q, Diggs LP, McVey JC, McCallen J, Wabitsch S, Ruf B, Brown Z, Heinrich B, Zhan Q, Rosato U, Wang S, Cui L, Berzofsky JA, KleinerDE, Bosco DB, Wu LJ, Lai CW, Rotman Y, Xie C, Korangy F, Greten TF
Cancer Cell. 40(9): 986-998, 2022. [ Journal Article ]