Microbiology and Immunology
Co-Leader of the Tumor Immunology & Immunotherapy Program (TII)
655 W Baltimore Street, BRB 10-045
Education and Training
Hebei Medical University, Shijiazhuang, China, MD, Medicine, 1994
Peking Union Medical College, Beijing, China, MS, Pharmacology, 1999
University of Florida, Gainesville, Florida, PhD, Cancer Biology, 2003
Washington University, Saint Louis, Missouri, Postdoctoral Fellow, Cancer Immunology, 2008
I received a medical degree in China and initially worked for two years as a resident in internal medicine. To pursue a research career with a goal to improve cancer treatment, I enrolled in PhD training at the University of Florida in Dr. Stratford May’s laboratory where I studied the biochemical pathways regulating cell death in the setting of blood cancers. I went on postdoctoral training in Dr. Timothy Ley’s laboratory at Washington University where I developed mouse models to study cancer immunology. I joined Roswell Park Cancer Institute as an assistant professor in 2008 and since established an independent laboratory that explores T cell biology using tumor and transplantation models. I moved to UMB in October 2017 as an associate professor in Microbiology and Immunology.
The scientific interests of my lab have been directed towards understanding the complexities of T cell biology and how T cells contribute to tumor immunity and transplantation immunity. We have focused on studying T cells in the setting of allogeneic hematopoietic cell transplantation (allo-HCT). Allo-HCT is a potentially curative treatment for blood cancers and other hematologic and immunologic diseases. However, graft-versus-host disease (GVHD) remains a major obstacle for more successful application of allo-HCT. GVHD is mediated by donor-derived T cells which recognize and damage genetically distinct normal host tissues. On the other hand, donor-derived T cells can protect the host from infection, and can also identify and attack host tumor cells, producing the beneficial graft-versus-tumor (GVT) effect. Current strategies for GVHD prevention and treatment are broadly immunosuppressive. Unfortunately, such strategies are not always successful, and may adversely affect immune reconstitution leading to infection or a reduced GVT effect that may result in cancer relapse or secondary malignancy. Therefore, our research aims at developing novel strategies that can prevent GVHD while balancing a reconstituted immune system capable of maintaining tumor immunosurveillance and infection immunity. To this end, we have focused on investigating the cellular and molecular mechanisms governing T cell differentiation, activation and effector function after allo-HCT. Specifically, we are studying cancer patients and mouse models to delineate the roles and mechanisms by which the beta2-adrenergic signaling pathway, the CD27/CD70 pathway, and the perforin/granzyme pathway impact the GVH and GVT responses. Our long-term goal is to develop immune-based therapies that are safe and effective for cancer patients.
Cancer immunology and immunotherapy, transplantation immunology, T cell biology, allogeneic hematopoietic cell transplantation (allo-HCT), graft-versus-host disease (GVHD)
Cao X, Cai SF, Fehniger TA, Song J, Collins LI, Piwnica-Worms D, Ley TJ. Granzyme B and perforin are important for regulatory T cell-mediated suppression of tumor clearance. Immunity. 2007 Oct; 27(4):635-46. PMID: 17919943
Bian G, Ding X, Leigh ND, Tang Y, Capitano ML, Qiu J, McCarthy PL, Liu H, Cao X. Granzyme B-mediated damage of CD8+ T cells impairs graft-versus-tumor effect. J Immunol. 2013 Feb 1;190 (3):1341-50. PMID: 23264653
Leigh ND, O’Neill RE, Du W, Chen C, Qiu J, Ashwell J, McCarthy PL, Chen G, Cao X. Host-derived CD70 suppresses murine GVHD by limiting donor T cell expansion and effector function. J Immunol. 2017 Jul 1;199(1):336-347. PMID: 28550198
O'Neill RE, Du W, Mohammadpour H, Alqassim E, Qiu J, Chen G, McCarthy PL, Lee KP, Cao X. T Cell-Derived CD70 Delivers an Immune Checkpoint Function in Inflammatory T Cell Responses. J Immunol. 2017 Nov 15;199(10):3700-3710. PMID: 29046346
Du W, Mohammadpour H, O'Neill RE, Kumar S, Chen C, Qiu M, Mei L, Qiu J, McCarthy PL, Lee KP, Cao X. Serine protease inhibitor 6 protects alloreactive T cells from Granzyme B-mediated mitochondrial damage without affecting graft-versus-tumor effect. Oncoimmunology. 2017 Nov 16;7(3):e1397247. PMID: 29399396
Mohammadpour H, O'Neil R, Qiu J, McCarthy PL, Repasky EA, Cao X. Blockade of Host β2-Adrenergic Receptor Enhances Graft-versus-Tumor Effect through Modulating APCs. J Immunol. 2018 Apr 1;200(7):2479-2488. PMID: 29445008
- Cao X, Deng X, May WS. Cleavage of Bax to p18 Bax accelerates stress-induced apoptosis, and a cathepsin-like protease may rapidly degrade p18 Bax. Blood. 2003 Oct 1;102(7):2605-14.
- Revell PA*, Grossman WJ*, Thomas DA*, Cao X*, Behl R*, Ratner JA. Lu ZH, Ley TJ. Granzyme B and the downstream granzymes C and/or F are important for cytotoxic lymphocyte functions. J Immunol. 2005 Feb 15;174(4):2124-31. (*Equal contribution).
- Fehniger TA, CaiSF, CaoX, BredemeyerAJ, PrestiRM, FrenchAR, Ley TJ. Acquisition of murine NK cell cytotoxicity requires the translation of a pre-existing pool of granzyme B and perforin mRNAs. Immunity. 2007 Jun;26(6):798-811.
- Cao X, Bennett RL, May WS. c-Myc and caspase-2 are involved in activating Bax during cytotoxic drug-induced apoptosis. J Biol Chem. 2008 May 23;283( 21):14490-96.
- Cai SF, Fehniger TA, Cao X, Mayer JC, Brune J, French A, Ley TJ. Differential expression of granzyme B and C in murine cytotoxic lymphocytes. J Immunol. 2009 May 15;182(10):6287-97.
- Cao X*, Leonard K, Collins LI, Cai SF, Mayer JC, Payton JE, Walter MJ, Piwnica-Worms D, Schreiber RD, Ley TJ. IL-12 stimulates interferon-gamma mediated inhibition of tumor-induced regulatory T cell proliferation and enhances tumor clearance. Cancer Res. 2009 Nov 15;69(22):8700-9 (*Correspondence author).
- Cao X. Regulatory T cells and immune tolerance to tumors. Immunol Res. 2010 Mar;46(1-3):79-93.
- Cai SF, Cao X, Hassan A, Fehniger TA, Ley TJ. Granzyme B is not required for regulatory T cell-mediated suppression of graft-versus-host disease. Blood. 2010 Mar 4;115(9):1669-77.
- Ding X, Bian G, Leigh ND, Qiu J, McCarthy PL, Liu H, Aygun-Sunar S, Burdelya LG, Gudkov AV, Cao X. A TLR5 agonist enhances CD8+ T cell-mediated graft-versus-tumor effect without exacerbating graft-versus-host disease. J Immunol. 2012 Nov 15; 189(10):4719-27.
- Leigh ND, Bian G, Ding X, Liu H, Aygun-Sunar S, Burdelya LG, Gudkov AV, Cao X. A Flagellin-derived Toll-like receptor 5 agonist stimulates cytotoxic lymphocyte-mediated tumor immunity. PLoS One. 2014 Jan 14;9(1):e85587.
- Du W, Leigh ND, Bian G, Mei L, O’Neill RE, Qiu J, Chen GL, Hahn T, Liu H, McCarthy PL, Cao X. Granzyme B-Mediated Activation-Induced Death of CD4+ T Cells Inhibits Murine Acute Graft-versus-Host Disease. J Immunol. 2015 Nov 1; 195(9):4514-23. PMID: 26392464 PMCID: PMC4610854
- Leigh ND, Kokolus K, Eng J, O’Neill RE, Du W, Qiu J, Chen G, McCarthy PL, Cao X*, Repasky E*. Housing Temperature-Induced Stress Is Suppressing Murine Graft-versus-Host Disease through beta2-Adrenergic Receptor Signaling. J Immunol. 2015 Nov 15; 195(10):5045-5054.(*Correspondence author) PMID: 26459348
- Bian G, Leigh ND, Du W, Zhang L, Li L, Cao X. Interferon‐Gamma Receptor Signaling Plays an Important Role in Restraining Murine Ovarian Tumor Progression. J Immunol Res Ther. 2016 April 28; 1(1): 15-21
- Du W, Leigh ND, Bian G, Alqassim E, O’Neill RE, Mei L, Qiu J, Liu H, McCarthy PL, Cao X. Granzyme B Contributes to the Optimal Graft-Versus-Tumor Effect Mediated by Conventional CD4+ T Cells. J Immunol Res Ther. 2016 April 30; 1(1): 22-28
- Kumar S, Mohammadpour H, Cao X. Targeting cytokines in GVHD therapy. J Immunol Res Ther. 2017;2(1):90-99.
- Ho, C. M., P. L. McCarthy, P. K. Wallace, Y. Zhang, A. Fora, P. Mellors, J. D. Tario, B. L. S. McCarthy, G. L. Chen, S. A. Holstein, S. R. Balderman, Cao X, B. Paiva, and T. Hahn. Immune signatures associated with improved progression-free and overall survival for myeloma patients treated with AHSCT. Blood Advances. 2017; 1: 1056-1066.
2008 Basic Research Fellow Scholar Award, American Society of Hematology
2010 Young Investigator Development Award, Roswell Park Alliance Foundation
2013 American Association of Immunologists Early Career Faculty Travel Award
2016 American Association of Immunologists Laboratory Travel Award
2016 American Association of Immunologists Careers in Immunology Fellowship Award
NIH/NCI, R01 CA184728 04/01/2015 – 03/31/2020
Title: Targeting Granzyme B to Separate GVH from GVL Responses
NIH/NCI, R21 CA202358 07/01/2016 – 06/30/2019
Title: Targeting Beta-Adrenergic Signaling to Control GVH and GVL Responses
NIH, R01 HL135325-01A1 06/01/2018 – 05/31/2023
Title: CD27/CD70 mediated negative regulation of inflammatory T cell responses