Binfeng Lu, PhD
- Postdoc, Yale University, 1998-2003
- PhD, Columbia University, 1998
- BS, Tsinghua University (Beijing), 1992
Associate Professor, Department of Immunology
Member, University of Pittsburgh Cancer Institute
Member, Graduate Program in Microbiology and Immunology (PMI)
The lab is interested in discovery of novel molecular and cellular pathways regulating key steps of T cell-mediated tissue-focused immune responses in antitumor immunity and autoimmunity. Such studies will shed new light on immunotherapy for cancer and autoimmune diseases.
Discovery of novel targets in tumor associated immune cells for improving T cell-mediated immunotherapy of cancer.
We are interested in discovering new targets for immunotherapy of cancer through studying the molecular basis underlying effective antitumor T cell immune responses in human and mice. We have found that IL-33R is up-regulated by T-bet and Eomes and 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. Although IL-33 and other cytokines such as IL-12 and IL-2 can inhibit tumor progression in mice, the cytokine-based approach has only achieved modest and transient antitumor effects in human. Therefore, another interest of ours is to understand what are the “brakes” that limit an otherwise successful cancer immunotherapy by cytokines. Our recent 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, we are interested in translating these new findings to the clinical setting, which should greatly benefit cancer patients.
Regulation of stress-triggered molecular responses in T cells in autoimmunity and cancer immunity.
ROS are important for T cells both as a second messenger and as a key inflammatory mediator within the cancer microenvironment and inflamed tissues. The molecular mechanisms underlying T cell responsiveness to ROS is unclear. In addition, how ROS shapes T-cell-mediated immune responses in vivo and how T cells adapt to high levels of ROS in inflamed tissues are largely unknown. We have recently found that ROS homeostasis in T cells is regulated by autophagy. This leads to our current interest in defining the role of autophagy in regulating ROS in T cells. We are also interested in studying the transcriptional factors induced by ROS in T cells as well as innate cells. Our current interest is to delineate key transcription factors in response to ROS in T cells and further understand how these transcription factors regulate T cell-mediated autoimmune responses and antitumor immune responses.
Autophagy is a critical intracellular process regulating T cell signaling, metabolism, clonal expanision and fate decision. Induction of autophagy is an important T cell response to changes of extracellular environments. Our lab has an established interest in understanding how autophagy is involved in physioloigcal and pathological T cell-mediated immune functions. Mechanistic studies of the autophagy regulated molecular network in T cells provide new insights to T cell Biology and immune related diseases.
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. doi:10.1038/ncomms13443. PubMed PMID: 27819653; PubMed Central PMCID: PMC5103075.
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. [Epub ahead of print] PubMed PMID: 26321222.
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. pii: 1401344. [Epub ahead of print] PMID: 25429071
Li G, Yang Q, Zhu Y, Wang HR, Chen X, Zhang X, Lu B. T-Bet and Eomes Regulate the Balance between the Effector/Central Memory T Cells versus Memory Stem Like T Cells. PLoS One. 2013 Jun 27;8(6):e67401. Print 2013. PubMed PMID: 23826287; PubMed Central PMCID: PMC3694876.
Tang Y, Xu X, Guo S, Zhang C, Tang Y, Tian Y, Ni B*, Lu B*, Wang H*, An increased abundance of tumor-infiltrating regulatory T cells is correlated with the progression and prognosis of pancreatic ductal adenocarcinoma. PLoS One. 2014 Mar 17;9(3):e91551. doi: 10.1371/journal.pone.0091551. eCollection 2014. PubMed PMID: 24637664; PubMed Central PMCID: PMC3956642. *co-corresponding authors.
Zeng T, Wang Q, Fu J, Lin Q, Bi J, Ding W, Qiao Y, Zhang S, Zhao W, Lin H, Wang M, Lu B, Deng X, Zhou D, Yin Z, Wang HR. Impeded Nedd4-1-mediated Ras degradation underlies Ras-driven tumorigenesis. Cell Rep. 2014 May 8;7(3):871-82. doi: 10.1016/j.celrep.2014.03.045. Epub 2014 Apr 17. PubMed PMID: 24746824.
Zhang L, Wu H, Lu D, Li G, Sun C, Song H, Li J, Zhai T, Huang L, Hou C, Wang W, Zhou B, Chen S, Lu B, Zhang X. The costimulatory molecule B7-H4 promote tumor progression and cell proliferation through translocating into nucleus. Oncogene. 2013 Nov 14;32(46):5347-58. doi: 10.1038/onc.2012.600. Epub 2013 Jan 14. PubMed PMID: 23318460; PubMed Central PMCID: PMC3898118.
Chen LJ, Zheng X, Shen YP, Zhu YB, Li Q, Chen J, Xia R, Zhou SM, Wu CP, Zhang XG, Lu BF*, Jiang JT*. Higher numbers of T-bet(+) intratumoral lymphoid cells correlate with better survival in gastric cancer. Cancer Immunol Immunother. 2013 Mar;62(3):553-61. doi: 10.1007/s00262-012-1358-6. Epub 2012 Oct 23. PubMed PMID:23090288.*co-corresponding authors.
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. Epub 2012 Feb 17. PubMed PMID: 22363469; PubMed Central PMCID: PMC3281852.
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. doi: 10.1002/eji.201141629. [Epub ahead of print] PMID: 21887788
Chen LJ, Sun J, Wu HY, Zhou SM, Tan Y, Tan M, Shan BE, Lu BF*, Zhang XG*. B7-H4 expression associates with cancer progression and predicts patient's survival in human esophageal squamous cell carcinoma. Cancer Immunol Immunother. 2011 Jul;60(7):1047-55. doi: 10.1007/s00262-011-1017-3. Epub 2011 Apr 26. PubMed PMID:21519829. *co-corresponding authors
Jiang J, Zhu Y, Wu C, Shen Y, Wei W, Chen L, Zheng X, Sun J, Lu B*, and Zhang X*, Tumor Expression of B7-H4 predicts poor Survival of Patients Suffering from Gastric Cancer. Cancer Immunology Immunotherapy 2010 Aug 20. [Epub ahead of print] PMID: 20725832. *corresponding author.
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. [Epub ahead of print]
Ju S, Zhu Y, Liu L, Dai S, Li C, Chen E, He Y, Zhang X, Lu B. Gadd45b and Gadd45g are important for anti-tumor immune responses. Eur J Immunol. 2009 Nov;39 (11):3010-8. PMID: 19688743
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. doi: 10.1038/cdd.2011.78. [Epub ahead of print]
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.