The Experts below are selected from a list of 11559 Experts worldwide ranked by ideXlab platform
George C Prendergast - One of the best experts on this subject based on the ideXlab platform.
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Indoleamine 2 3 dioxygenase and its therapeutic inhibition in cancer
International Review of Cell and Molecular Biology, 2018Co-Authors: Alexander J Muller, George C Prendergast, William P Malachowski, Arpita Mondal, Peggy ScherleAbstract:Abstract The tryptophan catabolic enzyme Indoleamine 2,3-dioxygenase-1 (IDO1) has attracted enormous attention in driving cancer immunosuppression, neovascularization, and metastasis. IDO1 suppresses local CD8 + T effector cells and natural killer cells and induces CD4 + T regulatory cells (iTreg) and myeloid-derived suppressor cells (MDSC). The structurally distinct enzyme tryptophan dioxygenase (TDO) also has been implicated recently in immune escape and metastatic progression. Lastly, emerging evidence suggests that the IDO1-related enzyme IDO2 may support IDO1-mediated iTreg and contribute to B-cell inflammed states in certain cancers. IDO1 and TDO are upregulated widely in neoplastic cells but also variably in stromal, endothelial, and innate immune cells of the tumor microenviroment and in tumor-draining lymph nodes. Pharmacological and genetic proofs in preclinical models of cancer have validated IDO1 as a cancer therapeutic target. IDO1 inhibitors have limited activity on their own but greatly enhance “immunogenic” chemotherapy or immune checkpoint drugs. IDO/TDO function is rooted in inflammatory programming, thereby influencing tumor neovascularization, MDSC generation, and metastasis beyond effects on adaptive immune tolerance. Discovery and development of two small molecule enzyme inhibitors of IDO1 have advanced furthest to date in Phase II/III human trials (epacadostat and navoximod, respectively). Indoximod, a tryptophan mimetic compound with a different mechanism of action in the IDO pathway has also advanced in multiple Phase II trials. Second generation combined IDO/TDO inhibitors may broaden impact in cancer treatment, for example, in addressing IDO1 bypass (inherent resistance) or acquired resistance to IDO1 inhibitors. This review surveys knowledge about IDO1 function and how IDO1 inhibitors reprogram inflammation to heighten therapeutic responses in cancer.
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Indoleamine 2 3 dioxygenase in t cell tolerance and tumoral immune escape
Immunological Reviews, 2008Co-Authors: Jessica B Katz, Alexander J Muller, George C PrendergastAbstract:Summary: Indoleamine 2, 3-dioxygenase (IDO) degrades the essential amino acid tryptophan in mammals, catalyzing the initial and rate-limiting step in the de novo biosynthesis nicotinamide adenine dinucleotide (NAD). Broad evidence implicates IDO and the tryptophan catabolic pathway in generation of immune tolerance to foreign antigens in tissue microenvironments. In particular, recent findings have established that IDO is overexpressed in both tumor cells and antigen-presenting cells in tumor-draining lymph nodes, where it promotes the establishment of peripheral immune tolerance to tumor antigens. In the normal physiologic state, IDO is important in creating an environment that limits damage to tissues due to an overactive immune system. However, by fostering immune suppression, IDO can facilitate the survival and growth of tumor cells expressing unique antigens that would be recognized normally as foreign. In preclinical studies, small-molecule inhibitors of IDO can reverse this mechanism of immunosuppression, complementing classical cytotoxic cancer chemotherapeutic agents' ability to trigger regression of treatment-resistant tumors. These results have encouraged the clinical translation of IDO inhibitors, the first of which entered phase I clinical trials in the fall of 2007. In this article, we survey the work defining IDO as an important mediator of peripheral tolerance, review evidence of IDO dysregulation in cancer cells, and provide an overview of the development of IDO inhibitors as a new immunoregulatory treatment modality for clinical trials.
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Indoleamine 2 3 dioxygenase in immune suppression and cancer
Current Cancer Drug Targets, 2007Co-Authors: Alexander J Muller, George C PrendergastAbstract:The extrahepatic enzyme Indoleamine 2,3-dioxygenase (IDO) catalyzes tryptophan degradation in the first and rate-limiting step towards biosynthesis of the central metabolic co-factor nicotinamide adenine dinucleotide (NAD). While this pathway has been known for decades, the actual physiological role for IDO in mammals remained obscure, because (i.) most cell types do not express the downstream enzymes in the NAD biosynthesis pathway and (ii.) mammals salvage rather than synthesize NAD to meet their metabolic needs. An immunological role for IDO was hinted at with the observation that IDO expression is stimulated by interferon- γ and subsequently confirmed by the discovery of its physiological importance in protecting the fetus from maternal immunity. Similarly, elevations in tryptophan catabolism in cancer patients were known since the 1950s, but the basis and meaning of this phenomenon were uncertain until it was shown that IDO, which is commonly elevated in tumors and draining lymph nodes, suppresses T cell immunity in the tumor microenvironment. Indeed, by creating peripheral tolerance to tumor antigens, IDO can undermine immune responses that thwart tumor cell survival in the context of an underlying inflammatory environment that facilitates tumor outgrowth. In preclinical studies, small molecule inhibitors of IDO compromise this mechanism of immunosuppression and strongly leverage the efficacy of a variety of classical chemotherapeutic agents, supporting the clinical development of IDO inhibitors as a therapeutic goal. This essay summarizes key findings that implicate IDO as an important mediator of peripheral tolerance and discusses the development of anti-cancer modalities that incorporate the use of IDO inhibitors.
Alexander J Muller - One of the best experts on this subject based on the ideXlab platform.
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Indoleamine 2 3 dioxygenase and its therapeutic inhibition in cancer
International Review of Cell and Molecular Biology, 2018Co-Authors: Alexander J Muller, George C Prendergast, William P Malachowski, Arpita Mondal, Peggy ScherleAbstract:Abstract The tryptophan catabolic enzyme Indoleamine 2,3-dioxygenase-1 (IDO1) has attracted enormous attention in driving cancer immunosuppression, neovascularization, and metastasis. IDO1 suppresses local CD8 + T effector cells and natural killer cells and induces CD4 + T regulatory cells (iTreg) and myeloid-derived suppressor cells (MDSC). The structurally distinct enzyme tryptophan dioxygenase (TDO) also has been implicated recently in immune escape and metastatic progression. Lastly, emerging evidence suggests that the IDO1-related enzyme IDO2 may support IDO1-mediated iTreg and contribute to B-cell inflammed states in certain cancers. IDO1 and TDO are upregulated widely in neoplastic cells but also variably in stromal, endothelial, and innate immune cells of the tumor microenviroment and in tumor-draining lymph nodes. Pharmacological and genetic proofs in preclinical models of cancer have validated IDO1 as a cancer therapeutic target. IDO1 inhibitors have limited activity on their own but greatly enhance “immunogenic” chemotherapy or immune checkpoint drugs. IDO/TDO function is rooted in inflammatory programming, thereby influencing tumor neovascularization, MDSC generation, and metastasis beyond effects on adaptive immune tolerance. Discovery and development of two small molecule enzyme inhibitors of IDO1 have advanced furthest to date in Phase II/III human trials (epacadostat and navoximod, respectively). Indoximod, a tryptophan mimetic compound with a different mechanism of action in the IDO pathway has also advanced in multiple Phase II trials. Second generation combined IDO/TDO inhibitors may broaden impact in cancer treatment, for example, in addressing IDO1 bypass (inherent resistance) or acquired resistance to IDO1 inhibitors. This review surveys knowledge about IDO1 function and how IDO1 inhibitors reprogram inflammation to heighten therapeutic responses in cancer.
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Indoleamine 2 3 dioxygenase in t cell tolerance and tumoral immune escape
Immunological Reviews, 2008Co-Authors: Jessica B Katz, Alexander J Muller, George C PrendergastAbstract:Summary: Indoleamine 2, 3-dioxygenase (IDO) degrades the essential amino acid tryptophan in mammals, catalyzing the initial and rate-limiting step in the de novo biosynthesis nicotinamide adenine dinucleotide (NAD). Broad evidence implicates IDO and the tryptophan catabolic pathway in generation of immune tolerance to foreign antigens in tissue microenvironments. In particular, recent findings have established that IDO is overexpressed in both tumor cells and antigen-presenting cells in tumor-draining lymph nodes, where it promotes the establishment of peripheral immune tolerance to tumor antigens. In the normal physiologic state, IDO is important in creating an environment that limits damage to tissues due to an overactive immune system. However, by fostering immune suppression, IDO can facilitate the survival and growth of tumor cells expressing unique antigens that would be recognized normally as foreign. In preclinical studies, small-molecule inhibitors of IDO can reverse this mechanism of immunosuppression, complementing classical cytotoxic cancer chemotherapeutic agents' ability to trigger regression of treatment-resistant tumors. These results have encouraged the clinical translation of IDO inhibitors, the first of which entered phase I clinical trials in the fall of 2007. In this article, we survey the work defining IDO as an important mediator of peripheral tolerance, review evidence of IDO dysregulation in cancer cells, and provide an overview of the development of IDO inhibitors as a new immunoregulatory treatment modality for clinical trials.
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Indoleamine 2 3 dioxygenase in immune suppression and cancer
Current Cancer Drug Targets, 2007Co-Authors: Alexander J Muller, George C PrendergastAbstract:The extrahepatic enzyme Indoleamine 2,3-dioxygenase (IDO) catalyzes tryptophan degradation in the first and rate-limiting step towards biosynthesis of the central metabolic co-factor nicotinamide adenine dinucleotide (NAD). While this pathway has been known for decades, the actual physiological role for IDO in mammals remained obscure, because (i.) most cell types do not express the downstream enzymes in the NAD biosynthesis pathway and (ii.) mammals salvage rather than synthesize NAD to meet their metabolic needs. An immunological role for IDO was hinted at with the observation that IDO expression is stimulated by interferon- γ and subsequently confirmed by the discovery of its physiological importance in protecting the fetus from maternal immunity. Similarly, elevations in tryptophan catabolism in cancer patients were known since the 1950s, but the basis and meaning of this phenomenon were uncertain until it was shown that IDO, which is commonly elevated in tumors and draining lymph nodes, suppresses T cell immunity in the tumor microenvironment. Indeed, by creating peripheral tolerance to tumor antigens, IDO can undermine immune responses that thwart tumor cell survival in the context of an underlying inflammatory environment that facilitates tumor outgrowth. In preclinical studies, small molecule inhibitors of IDO compromise this mechanism of immunosuppression and strongly leverage the efficacy of a variety of classical chemotherapeutic agents, supporting the clinical development of IDO inhibitors as a therapeutic goal. This essay summarizes key findings that implicate IDO as an important mediator of peripheral tolerance and discusses the development of anti-cancer modalities that incorporate the use of IDO inhibitors.
David H. Munn - One of the best experts on this subject based on the ideXlab platform.
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Indoleamine 2 3 dioxygenase and metabolic control of immune responses
Trends in Immunology, 2013Co-Authors: David H. Munn, Andrew L. MellorAbstract:Sustained access to nutrients is a fundamental biological need, especially for proliferating cells, and controlling nutrient supply is an ancient strategy to regulate cellular responses to stimuli. By catabolizing the essential amino acid TRP, cells expressing the enzyme Indoleamine 2,3 dioxygenase (IDO) can mediate potent local effects on innate and adaptive immune responses to inflammatory insults. Here, we discuss recent progress in elucidating how IDO activity promotes local metabolic changes that impact cellular and systemic responses to inflammatory and immunological signals. These recent developments identify potential new targets for therapy in a range of clinical settings, including cancer, chronic infections, autoimmune and allergic syndromes, and transplantation.
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Indoleamine 2 3 dioxygenase and tumor induced tolerance
Journal of Clinical Investigation, 2007Co-Authors: David H. Munn, Andrew L. MellorAbstract:Tumors arise from normal cells of the body through genetic mutation. Although such genetic mutation often leads to the expression of abnormal antigens, the immune system fails to respond effectively to these antigens; that is, it is tolerant of these antigens. This acquired state of tolerance must be overcome for cancer immunotherapy to succeed. Indoleamine 2,3-dioxygenase (IDO) is one molecular mechanism that contributes to tumor-induced tolerance. IDO helps create a tolerogenic milieu in the tumor and the tumor-draining lymph nodes, both by direct suppression of T cells and enhancement of local Treg-mediated immunosuppression. It can also function as an antagonist to other activators of antitumor immunity. Therefore, strategies to block IDO might enhance the effectiveness of tumor immunotherapy.
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Decreased protein nitration in macrophages that overexpress Indoleamine 2, 3-dioxygenase.
Cellular & Molecular Biology Letters, 2006Co-Authors: Derin B. Keskin, Brendan Marshall, David H. Munn, Andrew L. Mellor, Debra A. GearhartAbstract:The activity of Indoleamine 2, 3-dioxygenase (IDO; E.C. 1.13.11.42) catalyzes the oxidative cleavage of tryptophan to form kynurenine. IDO activity consumes superoxide anions; therefore, we postulated that over-expression of IDO might mitigate superoxide-anion dependent, oxidative modification of cellular proteins in vitro. We prepared and characterized RAW 264.7 macrophages that were stably transfected with either an IDO expression vector or the control (empty) vector. We detected IDO mRNA, protein, and enzyme activity in the IDO-transfected macrophages, but not in the macrophages transfected with the empty vector. To generate superoxide anions in situ, we treated the IDO-and control-transfected cultures with xanthine or hypoxanthine, and then used ELISA methods to quantitate the relative levels of oxidatively modified proteins in total cell lysates. The levels of protein carbonyls were similar in IDO-transfected and vector-transfected macrophages; however, protein nitration was significantly less in IDO-transfected cells compared to control transfectants. In addition, steady-state levels of superoxide anions were significantly lower in the IDO-transfected cultures compared with control transfectants. Our results are consistent with the concept that, besides degrading tryptophan, IDO activity may protect cells from oxidative damage.
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Indoleamine 2 3 dioxygenase tumor induced tolerance and counter regulation
Current Opinion in Immunology, 2006Co-Authors: David H. MunnAbstract:Tumors create an abnormal state of tolerance toward themselves and their antigens. One mechanism that might contribute to this tolerance is the immunoregulatory enzyme Indoleamine 2,3-dioxygenase (IDO). IDO-expressing antigen-presenting cells are found in tumor-draining lymph nodes, where they can create a tolerogenic microenvironment. IDO can also be expressed within the tumor itself, by tumor cells or host stromal cells, where it can inhibit the effector phase the immune response. Finally, emerging evidence suggests that IDO might also constitute a significant counter-regulatory mechanism, induced by clinically relevant pro-inflammatory signals, such as IFN-γ, IFN-α, CpG oligodeoxynucleotides, and 4-1BB ligation. Strategies to inhibit the IDO pathway may thus assist in breaking tolerance to tumors, and might enhance the efficacy of other immunotherapy strategies by removing unwanted counter-regulation.
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cells expressing Indoleamine 2 3 dioxygenase inhibit t cell responses
Journal of Immunology, 2002Co-Authors: Andrew L. Mellor, Derin B. Keskin, Theodore S Johnson, Phillip Chandler, David H. MunnAbstract:Pharmacological inhibition of Indoleamine 2,3-dioxygenase (IDO) activity during murine gestation results in fetal allograft rejection and blocks the ability of murine CD8 + dendritic cells to suppress delayed-type hypersensitivity responses to tumor-associated peptide Ags. These observations suggest that cells expressing IDO inhibit T cell responses in vivo. To directly evaluate the hypothesis that cells expressing IDO inhibit T cell responses, we prepared IDO-transfected cell lines and transgenic mice overexpressing IDO and assessed allogeneic T cell responses in vitro and in vivo. T cells cocultured with IDO-transfected cells did not proliferate but expressed activation markers. The potency of allogeneic T cell responses was reduced significantly when mice were preimmunized with IDO-transfected cells. In addition, adoptive transfer of alloreactive donor T cells yielded reduced numbers of donor T cells when injected into IDO-transgenic recipient mice. These outcomes suggest that genetically enhanced IDO activity inhibited T cell proliferation in vitro and in vivo. Genetic manipulation of IDO activity may be of therapeutic utility in suppressing undesirable T cell responses.
Andrew L. Mellor - One of the best experts on this subject based on the ideXlab platform.
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Indoleamine 2 3 dioxygenase and metabolic control of immune responses
Trends in Immunology, 2013Co-Authors: David H. Munn, Andrew L. MellorAbstract:Sustained access to nutrients is a fundamental biological need, especially for proliferating cells, and controlling nutrient supply is an ancient strategy to regulate cellular responses to stimuli. By catabolizing the essential amino acid TRP, cells expressing the enzyme Indoleamine 2,3 dioxygenase (IDO) can mediate potent local effects on innate and adaptive immune responses to inflammatory insults. Here, we discuss recent progress in elucidating how IDO activity promotes local metabolic changes that impact cellular and systemic responses to inflammatory and immunological signals. These recent developments identify potential new targets for therapy in a range of clinical settings, including cancer, chronic infections, autoimmune and allergic syndromes, and transplantation.
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Indoleamine 2 3 dioxygenase and tumor induced tolerance
Journal of Clinical Investigation, 2007Co-Authors: David H. Munn, Andrew L. MellorAbstract:Tumors arise from normal cells of the body through genetic mutation. Although such genetic mutation often leads to the expression of abnormal antigens, the immune system fails to respond effectively to these antigens; that is, it is tolerant of these antigens. This acquired state of tolerance must be overcome for cancer immunotherapy to succeed. Indoleamine 2,3-dioxygenase (IDO) is one molecular mechanism that contributes to tumor-induced tolerance. IDO helps create a tolerogenic milieu in the tumor and the tumor-draining lymph nodes, both by direct suppression of T cells and enhancement of local Treg-mediated immunosuppression. It can also function as an antagonist to other activators of antitumor immunity. Therefore, strategies to block IDO might enhance the effectiveness of tumor immunotherapy.
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Decreased protein nitration in macrophages that overexpress Indoleamine 2, 3-dioxygenase.
Cellular & Molecular Biology Letters, 2006Co-Authors: Derin B. Keskin, Brendan Marshall, David H. Munn, Andrew L. Mellor, Debra A. GearhartAbstract:The activity of Indoleamine 2, 3-dioxygenase (IDO; E.C. 1.13.11.42) catalyzes the oxidative cleavage of tryptophan to form kynurenine. IDO activity consumes superoxide anions; therefore, we postulated that over-expression of IDO might mitigate superoxide-anion dependent, oxidative modification of cellular proteins in vitro. We prepared and characterized RAW 264.7 macrophages that were stably transfected with either an IDO expression vector or the control (empty) vector. We detected IDO mRNA, protein, and enzyme activity in the IDO-transfected macrophages, but not in the macrophages transfected with the empty vector. To generate superoxide anions in situ, we treated the IDO-and control-transfected cultures with xanthine or hypoxanthine, and then used ELISA methods to quantitate the relative levels of oxidatively modified proteins in total cell lysates. The levels of protein carbonyls were similar in IDO-transfected and vector-transfected macrophages; however, protein nitration was significantly less in IDO-transfected cells compared to control transfectants. In addition, steady-state levels of superoxide anions were significantly lower in the IDO-transfected cultures compared with control transfectants. Our results are consistent with the concept that, besides degrading tryptophan, IDO activity may protect cells from oxidative damage.
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cells expressing Indoleamine 2 3 dioxygenase inhibit t cell responses
Journal of Immunology, 2002Co-Authors: Andrew L. Mellor, Derin B. Keskin, Theodore S Johnson, Phillip Chandler, David H. MunnAbstract:Pharmacological inhibition of Indoleamine 2,3-dioxygenase (IDO) activity during murine gestation results in fetal allograft rejection and blocks the ability of murine CD8 + dendritic cells to suppress delayed-type hypersensitivity responses to tumor-associated peptide Ags. These observations suggest that cells expressing IDO inhibit T cell responses in vivo. To directly evaluate the hypothesis that cells expressing IDO inhibit T cell responses, we prepared IDO-transfected cell lines and transgenic mice overexpressing IDO and assessed allogeneic T cell responses in vitro and in vivo. T cells cocultured with IDO-transfected cells did not proliferate but expressed activation markers. The potency of allogeneic T cell responses was reduced significantly when mice were preimmunized with IDO-transfected cells. In addition, adoptive transfer of alloreactive donor T cells yielded reduced numbers of donor T cells when injected into IDO-transgenic recipient mice. These outcomes suggest that genetically enhanced IDO activity inhibited T cell proliferation in vitro and in vivo. Genetic manipulation of IDO activity may be of therapeutic utility in suppressing undesirable T cell responses.
Yu-diao Kuan - One of the best experts on this subject based on the ideXlab platform.
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The inhibition of Indoleamine 2, 3-dioxygenase 1 by connexin 43.
International Journal of Medical Sciences, 2017Co-Authors: Chih-jen Yang, Yu-diao Kuan, Wei-kuang Wang, Wen-wei ChangAbstract:Upregulation of connexin 43 (Cx43) showed potential in enhancing immune surveillance that was suppressed in the tumor microenvironment. The expression of Indoleamine 2, 3-dioxygenase (IDO) is one of the crucial factors contributing to tumor immune tolerance by depletion of tryptophan and IDO-mediated tryptophan metabolites. Here, we aim to investigate the role of Cx43 in IDO production in murine tumor by using Cx43 inducers. Resveratrol (trans-3, 5, 4 '-trihydroxystilbene) is a natural plant-derived polyphenol possessing positive effect against cancer. Salmonella enterica serovar choleraesuis (S.C.) was proved to target and inhibit tumor growth. Both of them regulated Cx43 expression in tumor cells and led to either chemosensitizing or immune-activating. In this study, the correlation between Cx43 and IDO were determined by the treatment of resveratrol and S.C. Our data showed an increase in Cx43 while IDO protein and IDO-mediated inhibited effects on T cell decreased after tumor cells are given with resveratrol and S.C.All of which could be inhibited once the expression of Cx43 was blocked. Cx43 involved in IDO regulation might be useful in developing IDO-targeted cancer immune therapy.
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Salmonella overcomes tumor immune tolerance by inhibition of tumor Indoleamine 2, 3-dioxygenase 1 expression
Oncotarget, 2016Co-Authors: Yu-diao KuanAbstract:// Yu-Diao Kuan 1 , Che-Hsin Lee 1, 2 1 Graduate Institute of Basic Medical Science, School of Medicine, China Medical University, Taichung, Taiwan 2 Department of Microbiology, School of Medicine, China Medical University, Taichung, Taiwan Correspondence to: Che-Hsin Lee, e-mail: chlee@mail.cmu.edu.tw Keywords: salmonella, tumor-targeting, Indoleamine 2, 3-dioxygenase 1, immune tolerance Received: May 31, 2015 Accepted: October 22, 2015 Published: October 28, 2015 ABSTRACT Over the past decades, Salmonella has been proven capable of inhibiting tumor growth. It can specifically target tumors and due to its facultative anaerobic property, can be more penetrative than other drug therapies. However, the molecular mechanism by which Salmonella inhibits tumor growth is still incompletely known. The antitumor therapeutic effect mediated by Salmonella is associated with an inflammatory immune response at the tumor site and a T cell-dependent immune response. Many tumors have been proven to have a high expression of Indoleamine 2, 3-dioxygenase 1 (IDO), which is a rate-limiting enzyme that catalyzes tryptophan to kynurenine, thus causing immune tolerance within the tumor microenvironment. With decreased expression of IDO, increased immune response can be observed, which might be helpful when developing cancer immunotherapy. The expression of IDO was decreased after tumor cells were infected with Salmonella . In addition, Western blot analysis showed that the expression levels of phospho-protein kinase B (P-AKT), phospho-mammalian targets of rapamycin (P-mTOR), and phospho-p70 ribosomal s6 kinase (P-p70s6K) in tumor cells were decreased after Salmonella infection. In conclusion, our results indicate that Salmonella inhibits IDO expression and plays a crucial role in anti-tumor therapy, which might be a promising strategy combined with other cancer treatments.
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Abstract 1019: Salmonella break tumor immune tolerance by downregulation tumor Indoleamine 2, 3-dioxygenase 1 expression
Cancer Research, 2014Co-Authors: Yu-diao KuanAbstract:Over past decades, bacteria have been proven the capability of inhibiting tumor growth. It can specifically target tumor and due to its facultative anaerobe property, can be more penetrative than other drug therapies. However, the molecular mechanism that bacteria inhibit tumor growth is still incompletely known. Here we used Salmonella choleraesuis to investigate the mechanism. The antitumor therapeutic effect mediated by Salmonella is associated with an inflammatory immune response at tumor site and T helper 1-type immune response. Many tumors have been proven high expression of Indoleamine 2, 3-dioxygenase 1 (IDO), which is a rate-limiting enzyme that catalyzes tryptophan to kynurenine thus causing immunotolerance within tumor microenvironment. Our previous studies elucidated that Salmonella can also upregulate connexin 43 (CX43) to inhibit tumor progression and even enhance tumor chemosensitivity. Herein, we demonstrated that Salmonella can inhibit IDO expression through upregulation of CX43 in melanoma cells. Furthermore, we can also find the same phenomena in CX43 knock-down 4T1 and B16F10 cells. In brief, we point out that Salmonella-induced CX43 expression is a modulator of IDO expression and may play a crucial role in anti-tumor therapy, which combined with immunotherapy and Salmonella may be a prospective anti-tumor strategy. Citation Format: YU-DIAO KUAN, Che-Hsin Lee. Salmonella break tumor immune tolerance by downregulation tumor Indoleamine 2, 3-dioxygenase 1 expression. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1019. doi:10.1158/1538-7445.AM2014-1019