Update Your ProfileAcademic Title:
Associate Professor
Primary Appointment:
Microbiology and Immunology
Administrative Title:
Co-Leader of the Tumor Immunology & Immunotherapy Program (TII)
Location:
655 W Baltimore Street, BRB 10-045
Phone (Primary):
410-706-8452
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
Biosketch
The scientific interests of our lab have been directed towards understanding the complexities of T cell biology and how T cells contribute to tumor immunity and transplantation immunity. To this end, we focus on investigating the cellular and molecular mechanisms governing T cell development, differentiation, activation, and effector function. Specifically, we are interested in the co-stimulatory and co-inhibitory signals, sympathetic neurotransmitters, and cytotoxic pathways that are involved in the interactions among T cells, other immune cells and cancer cells in the setting of immune homeostasis, tumor progression and immune reconstitution after allogeneic hematopoietic cell transplantation. Our long-term goal is to develop immune-based therapies that are safe and effective for cancer patients. Currently we are studying cancer patients and mouse models, including syngeneic tumor models and allogeneic hematopoietic cell transplantation, to develop T cell-based and regulatory pathway-targeted cancer immunotherapies.
Research/Clinical Keywords
Cancer immunology and immunotherapy, transplantation immunology, T cell biology, allogeneic hematopoietic cell transplantation (allo-HCT), graft-versus-host disease (GVHD)
Highlighted Publications
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
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
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
Ciavattone NG, Wu L, O'Neill R, Qiu J, Davila E, Cao X. MyD88 co-stimulation in donor CD8+ T cells enhances the graft-versus-tumor effect in murine hematopoietic cell transplantation. J Immunol. 2021 Feb 15;206(4):892-903. PMID: 33408257
Tibbs E, Kandy RRK, Jiao D, Wu L, Cao X. Murine regulatory T cells utilize granzyme B to promote tumor metastasis. Cancer Immunol Immunother. 2023 Sep;72(9):2927-2937. doi: 10.1007/s00262-023-03410-w. Epub 2023 Feb 24. PubMed PMID: 36826509; PubMed Central PMCID: PMC10690887.
Puppala ER, Wu L, Fan X, Cao X. CD27 signaling inhibits tumor growth and metastasis via CD8 + T cell-independent mechanisms in the B16-F10 melanoma model. Cancer Immunol Immunother. 2024 Aug 6;73(10):198. doi: 10.1007/s00262-024-03780-9. PMID: 39105866
Additional Publication Citations
- 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.
- Kem WR, Mahnir VM, Prokai L, Papke RL, Cao X, LeFrancois S, Wildeboer K, Prokai-Tatrai K, Porter-Papke J, Soti F. Hydroxy metabolites of the Alzheimer's drug candidate 3-[(2,4-dimethoxy)benzylidene]-anabaseine dihydrochloride (GTS-21): their molecular properties, interactions with brain nicotinic receptors, and brain penetration. Mol Pharmacol. 2004 Jan;65(1):56-67.
- 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).
- Raja SM, Metkar SS, Honing S, Wang B, Russin WA, Pipalia NH, Menaa C, Belting M, Cao X, Dressel R, Froelich CJ. A novel mechanism for protein delivery: granzyme B undergoes electrostatic exchange from serglycin to target cells. J Biol Chem. 2005 May 27;280(21):20752-61.
- Fehniger TA, Cai SF, Cao X, Bredemeyer AJ, Presti RM, French AR, 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.
- 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
- 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 KM, O'Neill RE, Du W, Eng JW, Qiu J, Chen GL, McCarthy PL, Farrar JD, 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
- 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.
- 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.
- 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'Neill 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
- Mohammadpour H, Du W, O'Neill R, Khalili S, Qiu J, Repasky EA, McCarthy PL, Cao X. Host-Derived Serine Protease Inhibitor 6 Provides Granzyme B-Independent Protection of Intestinal Epithelial Cells in Murine Graft-versus-Host Disease. Biol Blood Marrow Transplant. 2018 Dec;24(12):2397-2408. PMID: 30006303
- Du W, Cao X. Cytotoxic Pathways in Allogeneic Hematopoietic Cell Transplantation. Front Immunol. 2018 Dec 19;9:2979. PMID: 30631325
- Kumar S, Leigh ND, Cao X. The Role of Co-stimulatory/Co-inhibitory Signals in Graft-vs.-Host Disease. Front Immunol. 2018 Dec 21;9:3003. PMID: 30627129
- O'Neill RE, Cao X. Co-stimulatory and co-inhibitory pathways in cancer immunotherapy. Adv Cancer Res. 2019;143:145-194. PMID: 31202358
- Wang W, Cao X. β-adrenergic signaling in tumor immunology and immunotherapy. Crit Rev Immunol. 2019;39(2):93-103. PMID: 31679250
- Paluskievicz CM, Cao X, Abdi R, Zheng P, Liu Y, Bromberg JS. T Regulatory Cells and Priming the Suppressive Tumor Microenvironment. Front Immunol. 2019 Oct 15;10:2453. PMID: 31681327
- Mahmood J, Alexander AA, Samanta S, Kamlapurkar S, Singh P, Saeed A, Carrier F, Cao X, Shukla HD, Vujaskovic Z. A Combination of Radiotherapy, Hyperthermia, and Immunotherapy Inhibits Pancreatic Tumor Growth and Prolongs the Survival of Mice. Cancers (Basel). 2020 Apr 21;12(4):1015. PMID: 32326142
- Mohammadpour H, Sarow JL, MacDonald CR, Chen GL, Qiu J, Sharma UC, Cao X, Herr MM, Hahn TE, Blazar BR, Repasky EA, McCarthy PL. β2-adrenergic receptor activation on donor cells ameliorates acute GvHD. JCI Insight. 2020 May 21:137788. PMID: 32437333
- Oba T, Hoki T, Yamauchi T, Keler T, Marsh HC, Cao X, Ito F. A Critical Role of CD40 and CD70 Signaling in Conventional Type 1 Dendritic Cells in Expansion and Antitumor Efficacy of Adoptively Transferred Tumor-Specific T Cells. J Immunol. 2020 Oct 1;205(7):1867-1877. PMID: 32848036
- Ciavattone NG, Wu L, O'Neill R, Qiu J, Davila E, Cao X. MyD88 co-stimulation in donor CD8+ T cells enhances the graft-versus-tumor effect in murine hematopoietic cell transplantation. J Immunol. 2021 Feb 15;206(4):892-903. PMID: 33408257
- Yamauchi T, Hoki T, Oba T, Kajihara R, Attwood K, Cao X, Ito F. CD40 and CD80/86 signaling in cDC1s mediate effective neoantigen vaccination and generation of antigen-specific CX3CR1+ CD8+ T cells. Cancer Immunol Immunother. 2021 May 26. doi: 10.1007/s00262-021-02969-6. PMID: 34037810
- Lutfi F, Wu L, Sunshine S, Cao X. Targeting the CD27-CD70 Pathway to Improve Outcomes in Both Checkpoint Immunotherapy and Allogeneic Hematopoietic Cell Transplantation. Front Immunol. 2021 Sep 22;12:715909. PMID: 34630390
- Tibbs E, Cao X. Murine myeloid derived suppressor cells possess a range of suppressive mechanisms - Granzyme B is not among them. Cancer Immunol Immunother. 2022 Feb 7. doi: 10.1007/s00262-022-03162-z. PMID: 35129637
- Tibbs E, Cao X. Emerging Canonical and Non-Canonical Roles of Granzyme B in Health and Disease. Cancers (Basel). 2022 Mar 10;14(6):1436. doi: 10.3390/cancers14061436. PMID: 35326588
- Sajjan S, Tibbs E, Utz M, Rapoport AP, Yared J, Dahiya S, Cao X, Hardy N, Sunshine SB. Can Janus kinase inhibition improve ocular graft versus host disease?. Ocul Surf. 2023 Apr;28:27-29. doi: 10.1016/j.jtos.2023.01.001. Epub 2023 Jan 10. PubMed PMID: 36634844; PubMed Central PMCID: PMC10683453.
- Thapa S, Cao X. Nervous regulation: beta-2-adrenergic signaling in immune homeostasis, cancer immunotherapy, and autoimmune diseases. Cancer Immunol Immunother. 2023 Aug;72(8):2549-2556. doi: 10.1007/s00262-023-03445-z. Epub 2023 Apr 15. Review. PubMed PMID: 37060364; PubMed Central PMCID: PMC10693916.
- Kalari Kandy RR, Fan X, Cao X. CD45.1/CD45.2 Congenic Markers Induce a Selective Bias for CD8+ T Cells during Adoptive Lymphocyte Reconstitution in Lymphocytopenia Mice. Immunohorizons. 2023 Nov 1;7(11):755-759. doi: 10.4049/immunohorizons.2300014. PubMed PMID: 37938184; PubMed Central PMCID: PMC10695411.
- Massalee R, Cao X. Repurposing beta-blockers for combinatory cancer treatment: effects on conventional and immune therapies. Front Pharmacol. 2023;14:1325050. doi: 10.3389/fphar.2023.1325050. eCollection 2023. Review. PubMed PMID: 38264530; PubMed Central PMCID: PMC10803533.
- Thompson R, Cao X. Reassessing Granzyme B: unveiling Perforin-independent versatility in immune responses and therapeutic potentials. Front Immunol. 2024 May 23;15: 1392535. doi: 10.3389/fimmu.2024.1392535. eCollection 2024. PMID: 38846935.
- Guasch FM, Sajjan S, Tibbs E, Reandeau C, Wu L, Bohlen J, Li A, Plotkin A, Cao X, Sunshine SB. CD3+ T cells in the Cornea of a Haploidentical Model of Ocular Graft Versus Host Disease. Ocul Surf. 2024 Jul;33:77-79. doi: 10.1016/j.jtos.2024.05.003. Epub 2024 May 31. PMID: 38823677
Awards and Affiliations
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
Grants and Contracts
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 06/01/2018 – 05/31/2023
Title: CD27/CD70 mediated negative regulation of inflammatory T cell responses
NIH, R01 HL159973 04/15/2022 – 03/31/2026
Title: Beta-2 adrenergic signaling in immune homeostasis and reconstitution