1120 15th Street CN 4141 Augusta, GA 30912 Office: (706) 721-7141 Appointments: (706) 721-8733 E-mail: dmunn@georgiahealth.edu

Munn, David, M.D.

David Munn, MD, pediatric oncologist, in his office at The GHSU Cancer Center.

Senior Advisor to the Cancer Center Director
Member, Cancer Immunology, Inflammation and Tolerance Program
GRU Cancer Center
Professor of Pediatrics

1120 15th Street, CN 4141
Phone: (706) 721-7141
DMUNN@ gru.edu

IFL Link | PubMed Link

Current Research

His current research focuses on tumor immunology, and molecular mechanisms of immune suppression and tolerance. Dr. Munn’s laboratory studies the regulation of T cell activation by tolerogenic dendritic cells and regulatory T cells (Tregs) in the setting of cancer.  A major focus of the laboratory is the immunoregulatory role of tryptophan metabolism via the enzyme indoleamine 2,3-dioxygenase (IDO).  Dr. Munn’s research is supported by grants from the National Cancer Institute, and through charitable endowments for pediatric oncology research.

Active projects include:

  • Preclinical and basic-science studies of the role of IDO-expressing plasmacytoid dendritic cells (pDCs) in tumor immunology, with an emphasis on how these tolerogenic antigen-presenting cells suppress anti-tumor immune responses via IDO and downstream pathways (AhR and GCN2).
  • Clinical/translational strategies (Phase I and II clinical trials) designed to enhance
    anti-tumor immune responses using IDO-inhibitor drugs.
  • Mechanistic studies of strategies to enhance anti-tumor immune response using vaccines
    in combination with inhibitors of immunosuppressive pathways (IDO, PD-1 and CTLA-4).
  • Control of regulatory T cell (Treg) suppressor activity by IDO, and functional activity of CD4+ helper T cells and reprogrammed Tregs.

Key References

Mellor AL, Munn DH. Creating immune privilege: active local suppression that benefits friends but protects foes. Nature Rev Immunol 2008;8:74-80.

Hou DY, Muller AJ, Sharma M, DuHadaway J, Banerjee T, Johnson M, Mellor AL, Prendergast GC, Munn DH. Inhibition of IDO in dendritic cells by stereoisomers of 1-methyl-tryptophan correlates with anti-tumor responses. Cancer Res 2007;67:792-801.

Munn DH, Mellor AL. Indoleamine 2,3-dioxygenase and tumor-induced tolerance. J Clin Invest 2007;117:1147-54.

Sharma MD, Baban B, Chandler P, Hou DY, Singh N, Yagita H, Azuma M, Blazar BR, Mellor AL, Munn DH. Plasmacytoid dendritic cells from mouse tumor-draining lymph nodes directly activate mature Tregs via indoleamine 2,3-dioxygenase. J Clin Invest 2007;117:2570-82.

Munn DH, Sharma MD, Baban B, Harding HP, Zhang Y, Ron D, Mellor AL. GCN2 kinase in T cells mediates proliferative arrest and anergy induction in response to indoleamine 2,3-dioxygenase. Immunity 2005;22:633-42.

Munn DH, Sharma MD, Hou D, Baban B, Lee JR, Antonia SJ, Messina JL, Chandler P, Koni PA, Mellor AL. Expression of indoleamine 2,3-dioxygenase by plasmacytoid dendritic cells in tumor-draining lymph nodes. J Clin Invest 2004;114:280-90.

Munn DH, Sharma M, Lee J, Jhaver KG, Johnson TS, Keskin DB, Marshall B, Chandler P, Antonia SJ, Burgess R, Slingluff CL Jr , Mellor AL. Potential regulatory function of human dendritic cells expressing indoleamine 2,3-dioxygenase. Science 2002;297:1867-70.

Munn DH, Zhou M, Attwood JT, Bondarev I, Conway S, Marshall B, Brown C, Mellor AL. Prevention of allogeneic fetal rejection by tryptophan catabolism. Science 1998;281:1191-93.

Grants (selected)

  • National Cancer Institute: “IDO-expressing immunoregulatory dendritic cells” 2003-2014, D. Munn, PI
  • National Cancer Institute: “Role of IDO malignancy” 2002-2012, D. Munn, PI
  • National Cancer Institute: “IDO-mediated immune regulation in established tumors” 2005-2014, D. Munn, PI
  • National Institutes of Health: “IDO dependent T cell suppression” 2005-2010, D. Munn, co-I
  • National Institutes of Health: “Manipulating natural host immunoregulation via IDO during viral infection” 2009-2014, D. Munn, co-I
  • Mason Trust Foundation: “Novel strategies for transplant tolerance” 2008-2011, D. Munn, co-I
  • Corn Foundation: “IDO in pediatric malignancies” 2005-2010 / D. Munn, PI

Grant information is updated quarterly.

 

Publications (selected)

member of editorial board:

  • Cancer Research

editorial reviewer:

  • Science
  • Immunity
  • Journal of Clinical Investigation
  • Blood
  • Journal of Experimental Medicine
  • Nature Immunology
  • Nature Medicine
  • Journal of Immunology
  • FASEB Journal

Mellor AL, Munn DH. Physiologic control of the functional status of Foxp3+ regulatory T cells. J Immunol (in press 2011).

Makala LH, Baban B, Lemos H, El-Awady AR, Chandler PR, Hou DY, Munn DH, Mellor AL. Leishmania major Attenuates Host Immunity by Stimulating Local Indoleamine 2,3-Dioxygenase Expression. J Infect Dis. 2011 Mar;203(5):715-25.

Antonov AS, Antonova GN, Munn DH, Mivechi N, Lucas R, Catravas JD, Verin AD. alphaVbeta3 Integrin Regulates Macrophage Inflammatory Responses via PI3-kinase/Akt-dependent NF-kappaB activation. J Cell Physiol. 2011 Feb;226(2):469-76.

Sharma MD, Hou DY, Baban B, Koni PA, He Y, Chandler PR, Blazar BR, Mellor AL, Munn DH. Reprogrammed foxp3(+) regulatory T cells provide essential help to support cross-presentation and CD8(+) T cell priming in naive mice. Immunity. 2010 Dec 14;33(6):942-54.

Highfill SL, Rodriguez PC, Zhou Q, Goetz CA, Koehn BH, Veenstra R, Taylor PA, Panoskaltsis-Mortari A, Serody JS, Munn DH, Tolar J, Ochoa AC, Blazar BR. Bone marrow myeloid-derived suppressor cells (MDSC) inhibit graft-versus-host (GVHD) disease via an arginase-1 dependent mechanism that is upregulated by IL-13. Blood. 2010 Dec 16;116(25):5738-47.

Zhou Q, Xiao H, Liu Y, Peng Y, Hong Y, Yagita H, Chandler P, Munn DH, Mellor A, Fu N, He Y. Blockade of programmed death-1 pathway rescues the effector function of tumor-infiltrating T cells and enhances the antitumor efficacy of lentivector immunization. J Immunol. 2010 Nov 1;185(9):5082-92.

Zhou Q, Munger ME, Highfill SL, Tolar J, Weigel BJ, Riddle M, Sharpe AH, Vallera DA, Azuma M, Levine BL, June CH, Murphy WJ, Munn DH, Blazar BR. Program death-1 (PD-1) signaling and regulatory T cells (Tregs) collaborate to resist the function of adoptively transferred cytotoxic T lymphocytes (CTLs) in advanced acute myeloid leukemia (AML). Blood. 2010 Oct 7;116(14):2484-93.

Metz R, Duhadaway JB, Rust S, Munn DH, Muller AJ, Mautino M, Prendergast GC. Zinc protoporphyrin IX stimulates tumor immunity by disrupting the immunosuppressive enzyme indoleamine 2,3-dioxygenase. Mol Cancer Ther. 2010 Jun;9(6):1864-71.

Johnson BA 3rd, Kahler DJ, Baban B, Chandler PR, Kang B, Shimoda M, Koni PA, Pihkala J, Vilagos B, Busslinger M, Munn DH, Mellor AL. B-lymphoid cells with attributes of dendritic cells regulate T cells via indoleamine 2,3-dioxygenase. Proc Natl Acad Sci U S A. 2010 Jun 8;107(23):10644-8.

Ding ZC, Blazar BR, Mellor AL, Munn DH, Zhou G. Chemotherapy rescues tumor-driven aberrant CD4+ T
cell differentiation and restores an activated polyfunctional helper phenotype. Blood. 2010. [In press]

Munn, D. H. Lineage-specific transcription factors in unexpected places. Eur J Immunol. 2010 Jan 26, 40: 315–317.

Sharma MD, Hou DY, Liu Y, Koni PA, Metz R, Chandler P, Mellor AL, He Y, Munn DH. Indoleamine 2, 3-dioxygenase controls conversion of Foxp3+ Tregs to TH17 -like cells in tumor-draining lymph nodes. Blood 113:6102-6111 (Jun, 2009).

Jasperson LK, Bucher C, Panoskaltsis-Mortari A, Mellor AL, Munn DH, Blazar BR. Inducing the tryptophan catabolic pathway, indoleamine 2,3-dioxygenase (IDO), for suppression of graft-versus-host disease (GVHD) lethality. Blood. 2009 Dec 3;114(24):5062-70.

Zhou Q, Bucher C, Munger ME, Highfill SL, Tolar J, Munn DH, Levine BL, Riddle M, June CH, Vallera DA, Weigel BJ, Blazar BR. Depletion of endogenous tumor-associated regulatory T cells improves the efficacy of adoptive cytotoxic T-cell immunotherapy in murine acute myeloid leukemia. Blood. 2009 Oct 29;114(18):3793-802.

Munn DH. Th17 cells in ovarian cancer. Blood. 2009 Aug 6;114(6):1134-5.

Baban B, Chandler PR, Sharma MD, Pihkala J, Koni PA, Munn DH, Mellor AL. IDO activates regulatory T cells and blocks their conversion into Th17-like T cells. J Immunol. 2009 Aug 15;183(4):2475-83.

Chung DJ, Rossi M, Romano E, Ghith J, Yuan J, Munn DH, Young JW. Indoleamine 2,3-dioxygenase-expressing mature human monocyte-derived dendritic cells expand potent autologous regulatory T cells. Blood. 2009 Jul 16;114(3):555-63.

Liu Y, Peng Y, Mi M, Guevara-Patino J, Munn DH, Fu N, He Y. Lentivector immunization stimulates potent CD8 T cell responses against melanoma self-antigen tyrosinase-related protein 1 and generates antitumor immunity in mice. J Immunol. 2009 May 15;182(10):5960-9.

Sharma MD, Hou DY, Liu Y, Koni PA, Metz R, Chandler P, Mellor AL, He Y, Munn DH. Indoleamine 2,3-dioxygenase controls conversion of Foxp3+ Tregs to TH17-like cells in tumor-draining lymph nodes. Blood. 2009 Jun 11;113(24):6102-11.

Kim YH, Choi BK, Kang WJ, Kim KH, Kang SW, Mellor AL, Munn DH, Kwon BS. IFN-gamma-indoleamine-2,3 dioxygenase acts as a major suppressive factor in 4-1BB-mediated immune suppression in vivo. J Leukoc Biol. 2009 May;85(5):817-25.

Muller AJ, Sharma MD, Chandler PR, DuHadaway JB, Everhart ME, Johnson BA III, Kahler DJ, Pihkala J, Soler AP, Munn DH, Pendergast GC, Mellor AL. Chronic inflammation that facilitates tumor progression creates local immune suppression by inducing indoleamine 2, 3 dioxygenase. Proc Nat Acad Sci 104:17073-17078 (2008).

Muller AJ, Sharma MD, Chandler PR, DuHadaway JB, Everhart ME, Johnson BA III, Kahler DJ, Pihkala J, Soler AP, Munn DH, Prendergast GC, Mellor AL. Chronic inflammation that facilitates tumor progression creates local immune suppression by inducing indoleamine 2,3 dioxygenase. Proc Natl Acad Sci USA. 2008 Nov 4;105(44):17073-8.

Chen W, Liang X, Peterson AJ, Munn DH, Blazar R. The indoleamine 2,3-dioxygenase pathway is essential for human plasmacytoid dendritic cell-induced adaptive T regulatory cell generation. J Immunol. 2008;181:5396-404.

Xu H, Oriss TB, Henry AC, Melgert BN, Chen L, Mellor AL, Munn DH, Irvin CG, Ray P, Ray A. A Role for Indoleamine 2,3-Dioxygenase in Lung Dendritic Cell Activation in Response to Allergens Impacting Allergic Airways Disease FASEB J. 2008 22: 670.9

Manches O, Munn DH, Fallahi A, Lifson J, Chaperot L, Plumas J, Bhardwaj N. HIV-activated plasmacytoid dendritic cells induce regulatory T cells through an indoleamine 2,3 dioxygenase dependent mechanism. J Clin Invest. 2008;118:3431-9.

Muller AJ, Sharma MD, Chandler PR, DuHadaway JB, Everhart ME, Johnson BA III, Kahler DJ, Pihkala J, Soler AP, Munn DH, Prendergast GC, Mellor AL. Chronic inflammation that facilitates tumor progression creates local immune suppression by inducing indoleamine 2,3 dioxygenase. Proc Nat Acad Sci. 2008;104:17073-8.

Manches O, Munn DH, Fallahi A, Lifson J, Chaperot L, Plumas J and Bhardwaj N. HIV-activated plasmacytoid dendritic cells induce regulatory T cells through an indoleamine 2,3 dioxygenase dependent mechanism. J Clin Invest. 2008;118:3431-9.

Muller AJ, Sharma MD, Chandler PR, DuHadaway JB, Everhart ME, Johnson BA III, Kahler DJ, Pihkala J, Soler AP, Munn DH, Prendergast GC and Mellor AL. Chronic inflammation that facilitates tumor progression creates local immune suppression by inducing indoleamine 2,3 dioxygenase. Proc Nat Acad Sci. 2008;104:17073-8.

Karunakaran S, Umapathy NS, Thangaraju M, Hatanaka T, Itagaki S, Munn DH, Prasad PD, Ganapathy V. Interaction of tryptophan derivatives with SLC6A14 (ATB(0,+)) reveals the potential of the transporter as a drug target for cancer chemotherapy. Biochem J. 2008 Sep 15;414(3):343-55.

Xu H, Oriss TB, Fei M, Henry AC, Melgert BN, Chen L, Mellor AL, Munn DH, Irvin CG, Ray P, Ray A. Indoleamine 2,3-dioxygenase in lung dendritic cells promotes Th2 responses and allergic inflammation. Proc Natl Acad Sci USA. 2008 May 6;105(18):6690-5.

Jasperson LK, Bucher C, Panoskaltsis-Mortari A, Taylor PA, Mellor AL, Munn DH, Blazar BR. Indoleamine 2,3-dioxygenase is a critical regulator of acute graft-versus-host disease lethality. Blood. 2008 Mar 15;111(6):3257-65.

Mellor AL, Munn DH. Creating immune privilege: active local suppression that benefits friends, but protects foes. Nat Rev Immunol. 2008 Jan;8(1):74-80. Review. Erratum in: Nat Rev Immunol. 2008 Feb;8(2):160.

Banerjee T, DuHadaway JB, Gaspari P, Sutanto-Ward E, Munn DH, Mellor AL, Malachowski WP, Prendergast GC, Muller AJ. A key in vivo antitumor mechanism of action of natural product-based brassinins is inhibition of indoleamine 2,3 dioxygenase.Oncogene. 2008 May 1;27(20):2851-7.

Publications are updated quarterly. For a complete listing, see Dr. Munn’s work on PubMed.

Book chapters:

Cheung NKV, Medof ME and Munn DH. (1988) Immunotherapy with GD2 specific monoclonal antibodies. In: Advances in Neuroblastoma Research 2 (eds. Evans AE, et al). Allan R. Liss, New York.
Munn DH, Cardon-Cardo C, Yeh SDJ, Kushner BH and Cheung NKV. (1989) Therapy of neuroblastoma with GD2 specific antibody 3F8. In: Gangliosides and Cancer (ed. Oettgen HF). VHC Verlagsgesellschaft mbH, Weinheim, West Germany.

Munn DH and Cheung NKV. (1990) Efficient killing of neuroblastoma cells by human monocytes activated with recombinant human macrophage colony-stimulating factor and antitumor antibody. In: Advances in Neuroblastoma Research 3 (eds. Evans, AE, et al). Wiley-Liss, New York.

Cheung NKV, Burch L, Kushner BH and Munn DH. (1990) Monoclonal antibody 3F8 can effect durable remissions in neuroblastoma patients refractory to chemotherapy: a phase II trial. In: Advances in Neuroblastoma Research 3 (eds. Evans AE, et al). Wiley Liss, New York.

Munn DH* and Cheung NKV. (1992) Pre-clinical and clinical studies of macrophage colony-stimulating factor. In: Seminars in Oncology (ed. Garnick MB). American Society of Clinical Oncology 19:395.

Gerrity RG, Antonov AS, Munn DH, Bell FP, Virmani R and Kolodgie FD. (1995) The macrophage in human and experimental atherosclerosis. In: Atherosclerosis X (eds. Woodford FP, et al). Elsevier Press, New York.

Schaub RG, Sypek JP, Kieth JC, Munn DH, Sherman ML, Dorner AJ and Garnick MB. (1998) Macrophage colony stimulating factor. In: Cytokines: Handbook of Immunopharmacology Series. Academic Press.

Munn DH*. (2006) Tumor immune evasion mediated by IDO. In: Cancer Chemotherapy and Biological Response Modifiers, Annual 23 (eds. Schilsky R, et al), published online as Update Cancer Ther 1:175-185.

Munn, DH*. (2009) Indoleamine 2,3-dioxygenase and tumor-induced immune suppression. In: Innate and Adaptive Immune Regulation and Cancer. (ed. Wang, RF). Springer, New York.

* denotes corresponding author

 

Affiliations

  • Professor, Pediatrics, Pathology, Cellular Biology and Anatomy, and College of Graduate Studies, Medical College of Georgia, Georgia Health Sciences University
  • Associate Professor, Medicine, Medical College of Georgia
  • Member, The GHSU MCG Immunotherapy Center
  • Member, Society for Pediatric Research