Cancer Immunology, Inflammation & Tolerance


David Munn

David Munn, MD

Cancer immunology, Inflammation and Tolerance Program
Professor, Pediatrics
Professor, Biochemistry and Molecular Biology
Professor, Cellular Biology and Anatomy
Professor, Medicine
Professor, Graduate Studies



Georgia Cancer Center
1410 Laney Walker Blvd., CN-4141
Phone: 706-721-8735
dmunn@augusta.edu 

Research Summary

Our research is focused on activating the body’s own immune system to fight cancer.  We work on discovering the ways in which cancers suppress the immune system, and on identifying the molecular mechanisms that tumors use to escape from immune attack.   Along with our collaborators, we have developed new drugs and clinical strategies to activate the immune response against tumors and enlist the patients’ own immune system to enhance the effectiveness of conventional chemotherapy drugs and radiation.  Target diseases include adult and pediatric solid tumors and leukemia’s.  Dr. Munn’s research is funded by the National Institutes of Health and support from charitable foundation donors.

Research Interests

Our research is focused on tumor immunology and the molecular mechanisms of immune suppression and tolerance in the tumor microenvironment.   The laboratory studies the regulation of anti-tumor T cell activation by tolerogenic dendritic cells and regulatory T cells (Tregs) in the setting of cancer.  Major focus areas in the laboratory include (i) activation of suppressive tumor-associated Tregs via the PTEN lipid-phosphatase pathway; (ii) regulation of the dendritic cell (DC) population in tumors and the choice between tolerogenic vs. immunogenic DCs; and (iii) tolerance-induction to dying tumor cells mediated via the enzyme indoleamine 2,3-dioxygenase (IDO) and PTEN+ Tregs.

Active projects include:

  • Basic-science studies of the role of the PTEN-phosphatase pathway in Tregs, including the regulation of the suppressor phenotype vs. destabilization and reprogramming during inflammation.  The translational goal of these studies is to develop orally-bioavailable small-molecule inhibitors drugs to block this novel immune-checkpoint and destabilize Tregs in tumors.
  • Molecular mechanisms of inflammation-induced differentiation of immunogenic dendritic cells, and the suppression of immunogenic DCs by PTEN+ Tregs.   The translational goal of these studies is to develop orally-bioavailable small-molecule drugs that induce differentiation of immunogenic DCs in tumors.
  • Basic and pre-clinical studies of immune response to dying tumor cells after chemotherapy; and synergy between conventional chemotherapy and novel forms of immunotherapy targeting Tregs and DCs.
  • Design and immune-monitoring of Phase I and Phase II clinical trials of IDO-inhibitor drugs in combination with chemotherapy, radiation and checkpoint blockade.  These include trials in both adult patients and first-in-children pediatric trials, in conjunction with the Pediatric Immunotherapy Service and Dr. Theodore Johnson

Selected Publications

Munn DH, Bronte V. Immune suppressive mechanisms in the tumor microenvironment. Curr Opin Immunol. 39:1-6 (2016).

Munn DH*, Mellor AL.  IDO in the Tumor Microenvironment: Inflammation, Counter-regulation and Tolerance. Trends Immunology 37(3):193-207 (Jan., 2016).

Johnson TS, Munn DH. Overcoming immune suppression in the tumor microenvironment: implications for multi-modal therapy. In: Gray JC, Marabelle A (Eds.)  Immunotherapy for Paediatric Malignancies. (chapter, in press): Springer, 2016.

Sharma MD, Shinde R, McGaha TL, Huang L, Holmgaard RB, Wolchok JD, Mautino MR, Celis E, Sharpe AH, Francisco LM, Powell JD, Yagita H, Mellor AL, Blazar BR, Munn DH.  The PTEN pathway in Tregs is a critical driver of the suppressive tumor microenvironment.  Science Advances  1, e1500845 (2015).

Lemos H, Huang L, Chandler PR, Mohamed E, Souza GR, Li L, Pacholczyk G, Barber GN, Hayakawa Y, Munn DH, Mellor AL. Activation of the STING Adaptor Attenuates Experimental Autoimmune Encephalitis. J Immunol. 192:5571-8 (2014).

Li M, Bolduc AR, Hoda MN, Gamble DN, Dolisca SB, Bolduc AK, Hoang K, Ashley C, McCall D, Rojiani AM, Maria BL, Rixe R, MacDonald TJ, Heeger PS, Mellor AL, Munn DH, Johnson TS.  The indoleamine 2,3-dioxygenase pathway controls complement-dependent enhancement of chemo-radiation therapy against murine glioblastoma. J Immunother Cancer JITC  2:21 (2014).

Ravishankar B, Shindea , Liu H, Chaudharya K, Bradleya J, Lemosa HP, Chandler P, Tanaka M, Munn DH, Mellor AL, McGaha TL.  Marginal zone CD169+ macrophages coordinate apoptotic cell-driven cellular recruitment and tolerance.  Proc Nat Acad Sci  111:4215-4220 (2014).

Munn DH, Mellor AL. Indoleamine 2,3-dioxygenase pathway: effect on Foxp3+ Tregs and cancer. In Prendergast GC and Jaffee EM (Eds) Cancer Immunotherapy: Immune Suppression and Tumor Growth, 2nd Edition. Elsevier (2013).

Munn DH, Mellor AL. Indoleamine 2,3 dioxygenase and metabolic control of immune responses. Trends Immunol 34:137-143 (2013).

Sharma MD, Huang L, Choi JH, Lee EJ, Wilson JM, Lemos H, Pan F, Blazar BR, Pardoll DM, Mellor AL, Shi H, Munn DH. An inherently bi-functional subset of Foxp3+ Treg/T-helper cells is controlled by the transcription factor Eos. Immunity 38:998-1012 (2013).

Holmgaard RB, Zamarin D, Munn DH, Wolchok JD and Allison JP. Indoleamine 2,3-dioxygenase is a critical resistance mechanism in anti-tumor T cell immunotherapy targeting CTLA-4. J Exp Med 210:1389-1402 (2013).

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. 33:942-54 (2010).

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 67:792-801 (2007).

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 Invest117:2570-82 (2007).

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 22:633-42 (2005).

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 114:280-90 (2004).

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 297:1867-70 (2002).

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 281:1191-93 (1998).

Johnson TS, Munn DH. Overcoming immune suppression in the tumor microenvironment: implications for multi-modal therapy. In: Gray JC, Marabelle A, editors. Immunotherapy for Paediatric Malignances: Springer, 2018

Sharma MD, Rodriguez PC, Koehn BH, Baban B, Cui Y, Guo G, et al. Activation of p53 in Immature Myeloid Precursor Cells Controls Differentiation into Ly6c(+)CD103(+) Monocytic Antigen-Presenting Cells in Tumors. Immunity 2018;48:91-106

Munn DH. The host protecting the tumor from the host - targeting PDL1 expressed by host cells. J Clin Invest 2018;128:570-2

Munn DH, Sharma MD, Johnson TS. Treg destabilization and reprogramming: implications for cancer immunotherapy. Cancer Res 2018;(in press)

Munn DH, Sharma MD, Johnson TS, Rodriguez P. IDO, PTEN-expressing Tregs and control of antigen-presentation in the murine tumor microenvironment. Cancer Immunol Immunother 2017;66:1049–58

Selected Grants

  • National Cancer Institute: “IDO-expressing immunoregulatory DCs” 2003-2019, PI: D.H. Munn
  • National Cancer Institute: “PTEN, Tregs and MDSCs in the tumor microenvironment” 2017-2022. PI: D.H. Munn
  • National Cancer Institute: “Chemo-radio-immunotherapy for pediatric brain tumors” (to start in 2019) co-PIs: D.H. Munn and T.S. Johnson
  • Corn Foundation: “IDO in pediatric malignancies”, 2006-2024, PI: D.H. Munn
  • Beloco Foundation: “Children’s Cancer Immunotherapy Program” 2013-2022, PI: D. H. Munn

Service

Member of editorial boards:

  • Cancer Immunology Research
  • Journal for Immunotherapy of Cancer (JITC)

Editorial reviewer:

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

Other Publications

Holmgaard RB, Zamarin D, Li Y, Gasmi B, Munn DH, Allison JP, Merghoub T, Wolchok JD.  Tumor-expressed IDO recruits and activates MDSCs in a Treg-dependent manner.  Cell Reports  13:412-424 (2015)

Hong Y, Manoharan I, Suryawanshi A, Majumdar T, Angus-Hill ML, Koni PA, Manicassamy B, Mellor AL, Munn DH, Manicassamy S. β-Catenin Promotes Regulatory T-cell Responses in Tumors by Inducing Vitamin A Metabolism in Dendritic Cells. Cancer Res. 75:656-665 (2015)

Suryawanshi A, Manoharan I, Hong Y, Swafford D, Majumdar T, Taketo MM, Manicassamy B, Koni PA, Thangaraju M, Sun Z, Mellor AL, Munn DH, Manicassamy S. Canonical wnt signaling in dendritic cells regulates Th1/Th17 responses and suppresses autoimmune neuroinflammation. J Immunol. 194:3295-304 (2015)

Ascierto PA, Munn DH, Palucka AK, Sondel PM. Highlights and Summary of the 28th Annual Meeting of the Society for Immunotherapy of Cancer. J Immunotherapy Cancer 2:15 (2014)

Singh N, Gurav A, Sivaprakasam S, Brady E, Padia R, Shi H, Thangaraju M, Prasad PD, Manicassamy S, Munn DH, Lee JR, Offermanns S, Ganapathy V. Regulation of colonic inflammation and carcinogenesis by Gpr109a, a G-protein-coupled receptor for niacin and the commensal metabolite butyrate. Immunity 40:128-139 (2014)

Liu H, Huang L, Bradley J, Liu K, Bardhan K, Ron D, Mellor AL, Munn DH, McGaha TL. GCN2-dependent metabolic stress is essential for endotoxemic cytokine induction and pathology. Mol Cell Biol 34:428-38 (2014)

Hong Y, Peng Y, Guo SZ, Guevara-Patino J, Pang J, Butterfield LH, Mivechi N, Munn DH, Bartlett DL, He Y. Epitope-optimized alpha-fetoprotein genetic vaccines prevent carcinogen-induced murine autochthonous hepatocellular carcinoma. Hepatology 59:1448–1458 (2014)

Ravishankara B, Shindea , Liu H, Chaudharya K, Bradleya J, Lemosa HP, Chandler P, Tanaka M, Munn DH, Mellor AL, McGaha TL. Marginal zone CD169+ macrophages coordinate apoptotic cell-driven cellular recruitment and tolerance. Proc Nat Acad Sci 111:4215-4220 (2014)

Sharma MD, Huang L, Choi JH, Lee EJ, Wilson JM, Lemos H, Pan F, Blazar BR, Pardoll DM, Mellor AL, Shi H, Munn DH. An inherently bi-functional subset of Foxp3+ Treg/T-helper cells is controlled by the transcription factor Eos. Immunity 38:998-1012 (2013)

Holmgaard RB, Zamarin D, Munn DH, Wolchok JD and Allison JP. Indoleamine 2,3-dioxygenase is a critical resistance mechanism in anti-tumor T cell immunotherapy targeting CTLA-4. J Exp Med 210:1389-1402 (2013)

Huang L, Li L, Lemos H, Chandler PR, Pacholczyk G, Baban B, Barber GN, Hayakawa Y, McGaha TL, Ravishankar B, Munn DH, Mellor AL. Cutting Edge: DNA sensing via the Stimulator of Interferon Genes (STING) adaptor in myeloid dendritic cells induces potent immune regulation via IDO1. J Immunol 191:3509-3513 (Aug., 2013)

Xiao H, Peng Y, Hong Y, Huang L, Guo ZS, Bartlett DL, Fu N, Munn DH, Mellor A, He Y. Local Administration of TLR Ligands Rescues the Function of Tumor-Infiltrating CD8 T Cells and Enhances the Antitumor Effect of Lentivector Immunization. J Immunol 190:5866-73 (2013)

Munn DH. Blocking IDO activity to enhance anti-tumor immunity. Frontiers Biosci 4:734-745 (2012)

Medzhitov R, Shevach EM, Trinchieri G, Mellor AL, Munn DH, Gordon S, Libby P, Hansson GK, Shortman K, Dong C, Gabrilovich D, Gabrysova L, Howes A, O’Garra A. Highlights of 10 years of immunology in Nature Reviews Immunology. Nat Rev Immunol 11:693-702 (2011)

Ding ZC, Huang L, Blazar B, Yagita H, Mellor AL, Munn DH, Zhou G. Polyfunctional CD4+ T cells are essential for eradicating advanced B-cell lymphoma after chemotherapy. Blood 120:2229-2239 (Sep., 2012)

Metz R, Rust S, DuHadaway JB, Mautino MR, Munn DH, Vahanian NN, Link CJ, Prendergast GC. IDO activation inhibits a tryptophan sufficiency signal needed to stimulate mTOR: a novel IDO effector pathway targeted by D-1-methyl-tryptophan. Oncoimmunology 1:1460-1468 (Dec. 2012)

Pei L, Choi JH, Liu J, Lee EJ, McCarthy B, Wilson JM, Speir E, Awan F, Tae H, Arthur G, Schnabel JL, Taylor KH, Wang X, Xu D, Ding HF, Munn DH, Caldwell C, Shi H. Genome-wide DNA methylation analysis reveals novel epigenetic changes in chronic lymphocytic leukemia. Epigenetics 7:567-578 (Jan., 2012)

Ravishankar B, Liu H, Shinde R, Chandler P, Baban B, Tanaka M, Munn DH, Mellor AL, Karlsson MCI, McGaha TL. Tolerance to apoptotic cells is regulated by indoleamine 2,3 dioxygenase. Proc Nat Acad Sci 109:3909-3914 (Feb., 2012)

Huang L, Lemos HP, Li L, Li M, Chandler PR, Baban B, McGaha TL, Ravishankar B, Lee JR, Munn DH, Mellor AL. Engineering DNA nanoparticles as immunomodulatory reagents that activate regulatory T cells. J Immunol 188:4913-4920 (May, 2012)

Hong Y, Peng Y, Mi M, Munn DH, Wang GQ, He Y.   Lentivector expressing HBsAg and immunoglobulin Fc fusion antigen induces potent immune responses and results in seroconversion in HBsAg transgenic mice. Vaccine 29:3909–3916 (Mar., 2011)

Baban B, Chandler PR, Johnson BA, Li M, Francisco LM, Sharpe AH, Blazar BR, Munn DH, Mellor AL. Physiologic control of regulatory T cell activation by dendritic cells expressing IDO. J Immunol 187: 2329–2335 (Aug., 2011)

Divanovic S, Sawtell NM, Trompette A, Warning JI, Dias A, Cooper AM, Yap GS, Arditi M, Shimada K, DuHadaway JB, Prendergast GC, Basaraba RJ, Mellor AL, Munn DH, Aliberti J, Karp CL. Opposing biological functions of tryptophan catabolizing enzymes during intracellular infection. J Inf Dis 205:152-161 (Jan., 2012)

Mellor AL, Munn DH. Physiologic control of the functional status of Foxp3+ regulatory T cells. J Immunol 186:4535-4540 (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 115: 2397 – 2406 (2010)

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.

1.   Johnson TS, Munn DH. Overcoming immune suppression in the tumor microenvironment: implications for multi-modal therapy. In: Gray JC, Marabelle A, editors. Immunotherapy for Paediatric Malignancies: Springer; 2018.

2.  Sharma MD, Rodriguez PC, Koehn BH, Baban B, Cui Y, Guo G, Shimoda M, Pacholczyk R, Shi H, Lee EJ, Xu H, Johnson TS, He Y, Mergoub T, Venable C, Bronte V, Wolchok JD, Blazar BR, Munn DH. Activation of p53 in Immature Myeloid Precursor Cells Controls Differentiation into Ly6c(+)CD103(+) Monocytic Antigen-Presenting Cells in Tumors. Immunity. 2018;48:91-106.

3.   Munn DH. The host protecting the tumor from the host - targeting PDL1 expressed by host cells. J Clin Invest. 2018;128:570-2.

4.  Munn DH, Sharma MD, Johnson TS. Treg destabilization and reprogramming: implications for cancer immunotherapy. Cancer Res. 2018;(in press).

5.  Munn DH, Sharma MD, Johnson TS, Rodriguez P. IDO, PTEN-expressing Tregs and control of antigen-presentation in the murine tumor microenvironment. Cancer Immunol Immunother. 2017;66:1049–58.

6.   Johnson TS, Aguilera D, Al-Basheer A, Castellino RC, Eaton BR, Esiashvili N, Foreman N, Heger IM, Kennedy EP, Link CJ, Martin W, Ring EK, Sadek RF, Smith A, Vahanian NN, MacDonald TJ, Munn DH, editors. Front-line therapy of DIPG using the IDO pathway inhibitor indoximod in combination with radiation and chemotherapy. American Association for Cancer Research (AACR) Annual Meeting; 2018; Chicago.

7.  Shinde R, Hezaveh K, Halaby MJ, Kloetgen A, Chakravarthy A, da Silva Medina T, Deol R, Manion KP, Baglaenko Y, Eldh M, Lamorte S, Wallace D, Chodisetti SB, Ravishankar B, Liu H, Chaudhary K, Munn DH, Tsirigos A, Madaio M, Gabrielsson S, Touma Z, Wither J, De Carvalho DD, McGaha TL. Apoptotic cell–induced AhR activity is required for immunological tolerance and suppression of systemic lupus erythematosus in mice and humans. Nat Immunol. 2018.

8.  Johnson TS, Aguilera D, Al-Basheer A, Eaton BR, Esiashvili N, Firat S, Fiveash JB, Foreman N, Fridlyand D, Friedman GK, Giller CA, Grosshans D, Heger IM, Kelly M, Kennedy EP, Kolhe RB, Liu A, Martin W, Mourad WF, Pacholczyk R, Parker R, Rojiani AM, Sadek RF, Vahanian NN, MacDonald TJ, Munn DH. Safety and tolerability of combining the IDO-inhibitor indoximod with re-irradiation for pediatric patients with progressive brain tumors treated on the NLG-2105 Phase 1 trial (NCT02502708). American Society of Pediatric Hematology Oncology Annual Meeting. 2017.

9.  Zakharia Y, McWilliams R, Shaheen M, Grossman K, Drabick J, Milhem M, Rixe O, Khleif S, Lott R, Kennedy E, Munn DH, Vahanian NN, Link C. Interim analysis of the Phase 2 clinical trial of the IDO pathway inhibitor indoximod in combination with pembrolizumab for patients with advanced melanoma.  American Association for Cancer Research Annual Meeting2017. p. Abstract CT117.

10. Noonepalle SK, Gu F, Lee EJ, Choi JH, Han Q, Kim J, Ouzounova M, Shull AY, Pei L, Hsu PY, Kohle R, Shi F, Choi J, Chiou K, Huang TH, Korkaya H, Deng L, Xin HB, Huang S, Thangaraju M, Sreekumar A, Ambs S, Tang SC, Munn DH, Shi H. Promoter Methylation Modulates Indoleamine 2, 3-dioxygenase 1 Induction by Activated T Cells in Human Breast Cancers. Cancer Immunol Res. 2017;5:330-44.

11. Emadi A, Holtzman N, Imran M, El Chaer F, Koka M, Singh Z, Shahlaee A, Sausville E, Law J, Lee S, Banerjee A, Rapoport A, Shi H, Kolhe R, Baer MR, Duong VH, Munn DH, Loken M, Kennedy E, Vahanian NN, Link C. Indoximod in combination with idarubicin and cytarabine for upfront treatment of patients with newly diagnosed acute myeloid leukemia: a Phase 1 report. Haematologica. 2017;102:375.

12.  Mangaonkar A, Mondal AK, Fulzule S, Pundkar C, Park EJ, Jillella A, Kota V, Xu H, Savage NM, Shi H, Munn D, Kolhe R. A novel immunohistochemical score to predict early mortality in acute myeloid leukemia patients based on indoleamine 2,3 dioxygenase expression. Sci Rep. 2017;7(1):12892.

13.   Ding Z-C, Habtetsion T, Cao Y, Li T, Liu C, Kuczma M, Chen T, Hao Z, Bryan L, Munn DH, Zhou G. Adjuvant IL-7 potentiates adoptive T cell therapy by amplifying and sustaining polyfunctional antitumor CD4+ T cells. Sci Rep. 2017;7(1):12168.

14.    Hippen KL, O'Connor RS, Lemire AM, Saha A, Hanse EA, Tennis NC, Merkel SC, Kelekar A, Riley JL, Levine BL, June CH, Turka LA, Kean LS, MacMillan ML, Miller JS, Wagner JE, Munn DH, Blazar BR. In Vitro Induction of Human Regulatory T Cells Using Conditions of Low Tryptophan Plus Kynurenines. Am J Transplant 2017.

15.    Johnson TS, Aguilera D, Al-Basheer A, Cooksey RM, Eaton BR, Esiashvili N, Firat S, Fiveash JB, Foreman N, Fridlyand D, Friedman GK, Giller CA, Grosshans DR, Heger IM, Kelly M, Kennedy EP, Knipstein J, Kolhe RB, Liu AK, Martin W, Mourad WF, Pacholczyk R, Parker R, Rojiani AM, Sadek RF, Thornton A, Vahanian NN, MacDonald T, Munn DH. Radio-immunotherapy using the IDO-inhibitor indoximod in combination with re-irradiation for children with progressive brain tumors in the phase 1 setting: an updated report of safety and tolerability (NCT02502708). Neuro-Oncology2017. p. vi185.

16.   Munn DH, Mellor AL. IDO in the Tumor Microenvironment: Inflammation, Counter-Regulation, and Tolerance. Trends Immunol. 2016;37:193-207.

17.   Munn DH, Bronte V. Immune suppressive mechanisms in the tumor microenvironment. Curr Opin Immunol. 2016;39:1-6.

18.    Sivaprakasam S, Gurav A, Paschall AV, Coe GL, Chaudhary K, Cai Y, Kolhe R, Martin P, Browning D, Huang L, Shi H, Sifuentes H, Vijay-Kumar M, Thompson SA, Munn DH, Mellor A, McGaha TL, Shiao P, Cutler CW, Liu K, Ganapathy V, Li H, Singh N. An essential role of Ffar2 (Gpr43) in dietary fibre-mediated promotion of healthy composition of gut microbiota and suppression of intestinal carcinogenesis. Oncogenesis. 2016;5:e238.

19.   Saha A, O'Connor RS, Thangavelu G, Lovitch SB, Dandamudi DB, Wilson CB, Vincent BG, Tkachev V, Pawlicki JM, Furlan SN, Kean LS, Aoyama K, Taylor PA, Panoskaltsis-Mortari A, Foncea R, Ranganathan P, Devine SM, Burrill JS, Guo L, Sacristan C, Snyder NW, Blair IA, Milone MC, Dustin ML, Riley JL, Bernlohr DA, Murphy WJ, Fife BT, Munn DH, Miller JS, Serody JS, Freeman GJ, Sharpe AH, Turka LA, Blazar BR. Programmed death ligand-1 expression on donor T cells drives graft-versus-host disease lethality. J Clin Invest. 2016;126:2642-60.

20.   Huang L, Ou R, Rabelo de Souza G, Cunha TM, Lemos H, Mohamed E, Li L, Pacholczyk G, Randall J, Munn DH, Mellor AL. Virus Infections Incite Pain Hypersensitivity by Inducing Indoleamine 2,3 Dioxygenase. PLoS Pathog. 2016;12:e1005615.

21.  Munn DH, Bronte V. Role of the Tumor Microenvironment. In: Butterfield LH, Kaufman HL, Marincola FM, editors. Cancer Immunotherapy: Principles and Practice. (in press): Demos; 2016.

22.   Zakharia Y, Drabick JJ, Khleif S, McWilliams RR, Munn DH, Link CJ, Vahanian NN, Kennedy E, Shaheen MF, Rixe O, Milhem MM. Updates on phase1b/2 trial of the indoleamine 2,3-dioxygenase pathway inhibitor indoximod plus checkpoint inhibitors for the treatment of unresectable stage 3 or 4 melanoma. ASCO Annual Meeting. 2016:(Abstract 3075).

23.   Lu Y, Hippen KL, Lemire AL, Gu J, Wang W, Ni X, Ranganathan P, Levine BL, Riley JL, June CH, Turka LA, Munn DH, Garzon R, Lu L, Blazar BR. miR-146b antagomir–treated human Tregs acquire increased GVHD inhibitory potency. Blood. 2016;128(10):1424-35.

24.   Ding ZC, Liu C, Cao Y, Habtetsion T, Kuczma M, Pi W, Kong H, Cacan E, Greer SF, Cui Y, Blazar BR, Munn DH, Zhou G. IL-7 signaling imparts polyfunctionality and stemness potential to CD4(+) T cells. Oncoimmunology. 2016;5:e1171445.

25.  McDonald-Hyman C, Flynn R, Panoskaltsis-Mortari A, Peterson N, MacDonald KP, Hill GR, Luznik L, Serody JS, Murphy WJ, Maillard I, Munn DH, Turka LA, Koreth J, Cutler CS, Soiffer RJ, Antin JH, Ritz J, Blazar BR. Therapeutic regulatory T-cell adoptive transfer ameliorates established murine chronic GVHD in a CXCR5-dependent manner. Blood. 2016;128:1013-7.

26. Hong Y, Manoharan I, Suryawanshi A, Shanmugam A, Swafford D, Ahmad S, Chinnadurai R, Manicassamy B, He Y, Mellor AL, Thangaraju M, Munn DH, Manicassamy S. Deletion of LRP5 and LRP6 in dendritic cells enhances antitumor immunity. Oncoimmunology. 2016;5:e1115941.

27.   Johnson TS, Giller CA, Heger IM, Kennedy EP, Kolhe RB, Mourad WF, Rojiani AM, Sadek RF, Vahanian NN, Macdonald TJ, Munn DH. Phase 1 trial of indoximod in combination with temozolomide-based therapy for children with progressive primary brain tumors (NCT02502708). Pediatr Blood Cancer. 2016;63(Suppl. 1):S72-S3.  Abstract from the 29th Annual Meeting of the American Society of Pediatric Hematology/Oncology (ASPHO), Minneapolis MN, May 2016.

28.   Zakharia Y, Munn D, Link C, Vahanian N, Kennedy E. Interim analysis of Phase 1b/2 combination of the IDO pathway inhibitor indoximod with temozolomide for adult patients with temozolomide-refractory primary malignant brain tumors. Neuro-Oncology. 2016;18(suppl. 6)(suppl 6):vi13-4.  Abstract from the 21st Annual Meeting of the Society for Neuro-Oncology (SNO), Scottsdale AZ, November 2016.

29.   Lemos H, Mohamed E, Huang L, Ou R, Pacholczyk G, Arbab AS, Munn D, Mellor AL. STING Promotes the Growth of Tumors Characterized by Low Antigenicity via IDO Activation. Cancer Res. 2016;76:2076-81.

Affiliations

  • Professor, Pediatrics, Pathology, Cellular Biology and Anatomy, and College of Graduate Studies, Medical College of Georgia, Augusta University