Binfeng Lu, PhD
Campus: 200 Lothrop St
Office: E1047 BSTWR
Pittsburgh, PA 15261
- Ph.D. - Columbia University (1998)
- Postdoc - Yale University (1998-2003)
- B.S. - Tsinghua University, Beijing (1992)
- Professor, Department of Immunology
- Member, University of Pittsburgh Cancer Institute
My research area includes tumor immunology and cancer immuotherapy. We are investigating ways to harness anti-tumor immune functions for clinical application. Our team has revealed immune checkpoint molecule expression on tumor associated Treg cells (TIM3+ Treg cells), established a key role of Tbet and Eomes in controlling memory stem T cells, ushered in novel cytokine-based cancer immune therapeutic approaches (IL-33 and IL-36), and pushed forward cytokine-based cancer drug development programs. The lab is currently interested in using data science for the discovery of novel molecular and cellular pathways regulating key steps of T cell-mediated tissue-focused immune responses in antitumor immunity and next-gen cancer immunotherapy.
Discovery of novel targets in tumor associated immune cells for improving T cell-mediated immunotherapy of cancer.
Our basic research is driven by biological Data science aiming at constructing and understanding the cellular and molecular immune networks in the tumor tissues. We are discovering new targets for immunotherapy of cancer through studying the molecular basis underlying effective antitumor T cell immune responses in human cancer.
We have found that the IL-33 receptor is up-regulated in effector Th1 and CD8 T cells. We further established that expression of IL-33 in tumor cells greatly inhibited tumor growth through enhancing the function of CD8 T cells and NK cells and inhibiting MDSC within tumor. Current interest is to explore IL-33 in immunotherapy of cancer and Mode of action by IL-33 class drugs in immune oncology.
Besides positive regulators of antitumor immune responses, we also have keen interest in understanding what are the “brakes” that limit an otherwise successful cancer immunotherapy. Our past work has identified several molecules that have such functions. We discovered that one such “immune brake” TIM-3 is highly expressed in tumor-infiltrating T cells in both human and mouse tumors. Blockade of TIM-3 should significantly improve immunotherapy of cancer. In close collaboration with clinicians and the biotech industry, we are actively involved in translating these new findings to the clinical setting, which should greatly benefit cancer patients.
Adaptive metabolic programing in T cells in autoimmunity and cancer immunity.
Our focus is on two major metabolic regulatory pathways namely Autophagy and the Integrated Stress Response pathway. Our studies have helped establish that these pathways are a critical intracellular process regulating T cell signaling, metabolism, clonal expansion and fate decision. Mechanistic studies of Beclin 1/Atg6 in autophagy and ATF4 in regulating amino acid metabolic reprogramming in T cells generate new insights to T cell Biology and immune related diseases.
Chen L, Sun R, Xu J, Zhai W, Zhang D, Yang M, Yue C, Chen Y, Li S, Turnquist H, Jiang J, Lu B. Tumor-Derived IL33 Promotes Tissue-Resident CD8+ T Cells and Is Required for Checkpoint Blockade Tumor Immunotherapy. Cancer Immunol Res. 2020 Nov;8(11):1381-1392. doi: 10.1158/2326-6066.CIR-19-1024. Epub 2020 Sep 11. PMID: 32917659; PMCID: PMC7642190. (Cover story).
Yang M, Giehl E, Feng C, Feist M, Chen H, Dai E, Liu Z, Ma C, Ravindranathan R, Bartlett D, Lu B*, and Guo Z*. *co-corresponding authors IL-36g-armed Oncolytic Virus Exerts Superior Efficacy through Induction of Potent Adaptive Antitumor Immunity. Cancer Immunology and Immunotherapy Cancer Immunol Immunother. 2021 Feb 4. doi: 10.1007/s00262-021-02860-4. PMID: 33538860. 2021.
Sun R, Wu Y, Zhou H, Wu Y, Yang Z, Gu Y, Jiang J, Lu B* and Zhu Y*. *co-corresponding authors. Eomes impedes durable response to tumor immunotherapy by inhibiting stemness, tissue residency, and promoting the dysfunctional state of intratumoral CD8+ T cells. Front Cell Dev Biol. 2021 Jan 21;9:640224. doi: 10.3389/fcell.2021.640224. eCollection 2021. PMID: 33553191. 2020
Guo W*, Wang Y*, Yang M*, Wang Z, Wang Y, Chaurasia S, Wu Z, Zhang M, Yadav G, Rathod S, Concha-Benavente F, Fernandez C, Li S, Xie W, Ferris R, Kammula U, Lu B, Yang D, *equal contribution. LincRNA-immunity landscape analysis identifies EPIC1 as a regulator of tumor immune evasion by inhibiting IFN-gamma-JAK-STAT1 signaling and antigen presentation. Sci Adv. 2021 Feb 10;7(7):eabb3555. doi:10.1126/sciadv.abb3555. Print 2021 Feb. PMID: 33568470
Yang M, Feng Y, Yue C, Xu B, Chen L, Jiang J, Lu B*, Zhu Y*. Lower expression level of IL-33 is associated with poor prognosis of pulmonary adenocarcinoma. PLoS One. 2018 Mar 2;13(3):e0193428.*co-corresponding authors.
Chen Y, Xia R, Huang Y, Zhao W, Li J, Zhang X, Wang P, Venkataramanan R, Fan J, Xie W, Ma X, Lu B, Li S. An immunostimulatory dual-functional nanocarrier that improves cancer immunochemotherapy. Nat Commun. 2016 Nov 7;7:13443.
Shi L, Chen L, Wu C*, Zhu Y, Xu B, Zheng X, Sun M, Wen W, Dai X, Yang M, Lv Q, Lu B*, Jiang J* PD-1 blockade boosts radiofrequency ablation-elicited adaptive immune responses against tumor. Clinical Cancer Research 2015 (In press) * corresponding authors.
Wang X, Zhao X, Feng C, Weinstein A, Xia R, Wen W, Lv Q, Zuo S, Tang P, Yang X, Chen X, Wang H, Zang S, Stollings L, Denning TL, Jiang J, Fan J, Zhang G, Zhang X, Zhu Y, Storkus W, Lu B. IL-36γ Transforms the Tumor Microenvironment and Promotes Type 1 Lymphocyte-Mediated Antitumor Immune Responses. Cancer Cell. 2015 Aug 26. pii: S1535-6108(15)00266-4. doi: 10.1016/j.ccell.2015.07.014.
Gao X, Wang X, Yang Q, Zhao X, Wen W, Li G, Lu J, Qin W, Qi Y, Xie F, Jiang J, Wu C, Zhang X, Chen X, Turnquist H, Zhu Y, Lu B. Tumoral Expression of IL-33 Inhibits Tumor Growth and Modifies the Tumor Microenvironment through CD8+T and NK Cells. J Immunol. 2014 Nov 26.
Gao X, Zhu Y, Li G, Huang H, Zhang G, Wang F, Sun J, Yang Q, Zhang X, Lu B. TIM-3 expression characterizes regulatory T cells in tumor tissues and is associated with lung cancer progression. PLoS One. 2012;7(2):e30676. doi: 10.1371/journal.pone.0030676.
Yang Q, Li G, Zhu Y, Liu L, Chen E, Turnquist H, Zhang X, Finn OJ, Chen X, Lu B. IL-33 synergizes with TCR and IL-12 signaling to promote the effector function of CD8(+) T cells. Eur J Immunol. 2011 Sep 2.
Zhu Y, Ju S, Chen E, Dai S, Li C, Morel P, Liu L, Zhang X, Lu B. T-bet and Eomesodermin Are Required for T Cell-Mediated Antitumor Immune Responses. J Immunol. 2010 Aug 16.
Adaptive metabolic programing in T cells
Yang X, Xia R, Yue C, Zhai W, Du W, Yang Q, Cao H, Chen X, Obando D, Zhu Y, Chen X, Chen JJ, Piganelli J, Wipf P, Jiang Y, Xiao G, Wu C, Jiang J, Lu B. ATF4 Regulates CD4(+) T Cell Immune Responses through Metabolic Reprogramming. Cell Rep. 2018 May 8;23(6):1754-1766.
Kovacs J, Yang Q, Gonzalez-García I, Li C, Ju S, Gonzales-Garcia I, Chen X, Zhang X, and Lu B, Autophagy promotes T cell survival through degradation of proteins of the cell death machinery. Cell Death and Differentiation 2011 Jun 10.
Li C, Capan E, Zhao Y, Zhao J, Stolz D, Watkins S, Jin S, Lu B. Autophagy is induced in CD4+ T cells and important for the growth factor-withdrawal cell death. The Journal of Immunology 2006 Oct 15;177(8):5163-8.