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Eduardo  Davila

Eduardo Davila Ph.D.

Academic Title: Associate Professor
Primary Appointment: Microbiology and Immunology
Additional Title(s): Program Leader, Tumor Immunology and Immunotherapy Program, UMGCC
Location: Bressler Research Building, 10-050
Phone: (410) 706-5051
Lab: (410) 706-5049

Research Interests:

Dr. Davila is the Program Leader for the Tumor Immunology and Immunotherapy Program within the University of Maryland Marlene and Stewart Greenebaum Cancer Center Program. As such, he collaborates with both basic and clinical research investigators to understand the immune regulation of malignant disease and translate this knowledge into the development of novel diagnostic, preventative and treatment regimens. Dr. Davila’s research centers on the projects below.

Exploiting TLR signaling in T cells for enhanced anti-tumor activity (Project 1)
Supported by R01CA140917 and by P20RR021970

T cell-based therapies for cancer in the form of adoptive T cell transfer (ACT) or cancer vaccines can kill tumors expressing immunodominant tumor antigens (TA). However, this process allows the escape of tumor cells expressing poorly immunogenic or subdominant TAs. These cells can reestablish the tumor and metastasize, ultimately killing the host. We are currently addressing several of the most significant hurdles in developing T cell-based immunotherapy and propose innovative ways to circumvent these challenges.

We have genetically modified human T cells to express a tumor-specific TCR and to produce the TLR5 ligand. We are testing the hypothesis that tumor-reactive T cells will generate potent and long-lived antitumor activity by co-stimulating both tumor-specific T cells and antigen presenting cells at the tumor site via production of TLR ligands within the tumor microenvironment. In these experiments, we use a physiologically relevant human-to-mouse model that allows a detailed evaluation of the in vivo responses of tumor-specific CD8 T cells against melanoma tumors in the brain.

We are also focused on defining the signaling pathway through which TLR2-MyD88 signals within tumor-reactive CD8 T cells potentiate activation to a poorly immunogenic tumor antigen. Our current indicate that the costimulatory effects of MyD88 signaling in T cells is regulated in large part by the mammalian target of rapamycin (MTOR). Furthermore, research efforts have led to examine the three specific miRNAs which appear to regulate MyD88 signaling in T cells.

Pattern recognition receptors and T-cell leukemia progression (Project 2)
Supported by a grant from the Leukemia and Lymphoma Society

Our long-term objective for this project is to understand the role of dysregulated TLR-MyD88-IRAK signaling in the pathogenesis of T-cell acute lymphoblastic leukemia (T-ALL) and to develop novel diagnostic, prognostic, and therapies to treat patients. Recent studies highlight a previously unappreciated role for pattern recognition receptor (PRR) signaling (i.e. toll-like receptors, TLR) on T-cells and their effects on survival and proliferation. PRRs can bind exogenous molecules derived from pathogens as well as endogenous ligands released from stressed or dying cells. Our published reports on primary T-cells and our preliminary data using T-cell leukemia lines and samples from patients with T-ALL indicate that direct stimulation of PRRs enhances cell proliferation and survival.

We seek to understand the prevalence and physiological significance of PRR signaling in neoplastic T-cells. We are also examining the therapeutic efficacy of inhibiting TLR-MyD88-IRAK signaling with or without chemotherapy in vivo. For these studies we use patient-derived T-ALL cells transferred into the immune-compromised Nod-Scid mice.

Grants & Contracts:

Supported by R01CA140917, P20RR021970, Leukemia and Lymphoma Society, and the University of Maryland Greenebaum Cancer Center


TLR5 Ligand-Secreting T Cells Reshape the Tumor Microenvironment and Enhance Antitumor Activity. Geng D, Kaczanowska S, Tsai A, Younger K, Ochoa A, Rapoport AP, Ostrand-Rosenberg S, Davila E. Cancer Res. 2015 Mar 20. [Epub ahead of print] PMID:25795705

Inhibition of IRAK1/4 sensitizes T cell acute lymphoblastic leukemia to chemotherapies. Li Z, Younger K, Gartenhaus R, Joseph AM, Hu F, Baer MR, Brown P, Davila E. J Clin Invest. 2015 Mar 2;125(3):1081-97. doi: 10.1172/JCI75821. Epub 2015 Feb 2. PMID:25642772

IL-1 Receptor-Associated Kinase Signaling and Its Role in Inflammation, Cancer Progression, and Therapy Resistance. Jain A, Kaczanowska S, Davila E. Front Immunol. 2014 Nov 17;5:553. doi: 10.3389/fimmu.2014.00553. eCollection 2014. Review. PMID:25452754

Eomesodermin is required for antitumor immunity mediated by 4-1BB-agonist immunotherapy. Song C, Sadashivaiah K, Furusawa A, Davila E, Tamada K, Banerjee A. Oncoimmunology. 2014 Jan 1;3(1):e27680. Epub 2014 Feb 27. PMID:24790793

A high throughput method for enrichment of natural killer cells and lymphocytes and assessment of in vitro cytotoxicity. So EC, Sallin MA, Zhang X, Chan SL, Sahni L, Schulze DH, Davila E, Strome SE, Jain A. J Immunol Methods. 2013 Aug 30;394(1-2):40-8. doi: 10.1016/j.jim.2013.05.001. Epub 2013 May 13. PMID:23680234

Cod glycopeptide with picomolar affinity to galectin-3 suppresses T-cell apoptosis and prostate cancer metastasis. Guha P, Kaptan E, Bandyopadhyaya G, Kaczanowska S, Davila E, Thompson K, Martin SS, Kalvakolanu DV, Vasta GR, Ahmed H. Proc Natl Acad Sci U S A. 2013 Mar 26;110(13):5052-7. doi: 10.1073/pnas.1202653110. Epub 2013 Mar 11. PMID:23479624

TLR agonists: our best frenemy in cancer immunotherapy. Kaczanowska S, Joseph AM,    Davila E. J Leukoc Biol. 2013 Jun;93(6):847-63. doi: 10.1189/jlb.1012501. Epub 2013 Mar 8. Review. PMID:23475577

Augmentation of therapeutic responses in melanoma by inhibition of IRAK-1,-4. Srivastava R, Geng D, Liu Y, Zheng L, Li Z, Joseph MA, McKenna C, Bansal N, Ochoa A, Davila E. Cancer Res. 2012 Dec 1;72(23):6209-16. doi: 10.1158/0008-5472.CAN-12-0337. Epub 2012 Oct 4. PMID:23041547

Redirecting gene-modified T cells toward various cancer types using tagged antibodies. Tamada K, Geng D, Sakoda Y, Bansal N, Srivastava R, Li Z, Davila E. Clin Cancer Res. 2012 Dec 1;18(23):6436-45. doi: 10.1158/1078-0432.CCR-12-1449. Epub 2012 Oct 2. Erratum in: Clin Cancer Res. 2013 Feb 15;19(4):951. PMID:23032741