Our Approach
Targeting major metabolic networks that are disrupted in the tumor microenvironment and contribute to immunosuppression.

Our Approach

Pioneering the next frontier in cancer immunotherapy

Despite the increasing use of immuno-oncology drugs and targeted therapies, complete and durable responses are observed in only a subset of patients; and most patients’ cancers advance even while receiving therapy. With the aim of improving current standard of care, we are developing our therapeutic candidates as monotherapies and in combination with approved drugs with the goal of curing cancer.

The more fundamental a role in immune suppression a metabolite plays, the more likely it is to be an effective therapeutic target across multiple tumor types, ultimately benefiting more patients. Therefore, our research focuses on immuno-metabolic pathways which have the potential to impact both the adaptive and innate immune system relevant in a broad range of tumor types.

Activation of metabolic pathways can lead to a number of local changes that promote tumor survival. These immune suppressive pathways have broad effects including decreased T cell expansion and tumor infiltration and increased immune suppressor cells such as myeloid-derived suppressor cells (MDSCs) and T regulatory cells.

What is an immunosuppressive metabolite?

Immunosuppressive metabolites are molecules that are formed by a breakdown of a ‘precursor’ that function to suppress an immune response. These metabolites inhibit the activity of effector immune cells such as cytotoxic T-cells or by increasing the activity of regulatory immune cells such as myeloid-derived suppressor cells. Multiple metabolic pathways are upregulated in cancer leading to increased concentrations of immunosuppressive metabolites enabling cancer cells to evade recognition of effector immune cells.

Common characteristics of an immunosuppressive tumor microenvironment


  • Secretion of immunosuppressive molecules
  • Generation of immunosuppressive metabolites
  • Infiltration of regulatory immune cells
  • Incidence of anergic effector T cells


  • Expression of immune-activating molecules
  • Penetration of proinflammatory helper and effector immune cells
  • Tumor antigen presentation

Tackling the protective tumor micro-environment

Tumors cause a number of structural and chemical changes in the surrounding area, referred to as the “tumor micro-environment” or TME. These changes in the surrounding cells and tissues promote tumor survival. At Kyn Therapeutics, we are focused on reversing these changes to enhance immunity, and allow responding immune cells to reach the tumor.

Key publications in immunometabolism

Research by Kyn team members and collaborators

Control of tumor-associated macrophages and T cells in glioblastoma via AHR and CD39

Takenaka, M. et al. (2019)
Nature Neuroscience

Inhibiting IDO pathways to treat cancer: lessons from the ECHO-301 trial and beyond

Muller, A. J., Manfredi, M. G., Zakharia, Y. and Prendergast, G. C. (2018)
Seminars in Immunopathology

Reversal of indoleamine 2,3-dioxygenase–mediated cancer immune suppression by systemic kynurenine depletion with a therapeutic enzyme

Triplett, T. et al. (2018)
Nature Biotechnology

Discovery of IDO1 Inhibitors: From Bench to Bedside

Prendergast, G., Malachowski, W., DuHadaway, J. and Muller, A. (2017)
Cancer Research Reviews

IDO in the Tumor Microenvironment: Inflammation, Counter-Regulation, and Tolerance

Munn, D. and Mellor, A. (2016)
Trends in Immunology

Big opportunities for small molecules in immuno-oncology

Adams, J. L., Smothers, J., Srinivasan, R. and Hoos, A. (2015)
Nature Reviews Drug Discovery

Aryl hydrocarbon receptor ligands in cancer: friend and foe

Murray, I., Patterson, A. and Perdew, G. (2014)
Nature Reviews Cancer

Regulation of Immune Responses by Prostaglandin E2

Kalinski, P. (2012)
The Journal of Immunology

Other supporting literature

The Aryl hydrocarbon receptor mediates tobacco-induced PD-L1 expression and is associated with response to immunotherapy

Wang, G. et al. (2019)
Nature Communications

Tumor-Repopulating Cells Induce PD-1 Expression in CD8+ T Cells by Transferring Kynurenine and AhR Activation

Liu, Y. et al. (2018)
Cancer Cell

Targeting the IDO1/TDO2–KYN–AhR Pathway for Cancer Immunotherapy – Challenges and Opportunities

Cheong, J. and Sun, L. (2017)
Trends in Pharmacological Sciences

The role of prostaglandin E2 in tumor associated immunosuppression

Wang, D. and DuBois, R. N. (2016)
Trends in Molecular Medicine

Cancer Immunotherapy by Targeting IDO1/TDO and Their Downstream Effectors

Platten, M., von Knebel Doeberitz, N., Oezen, I., Wick, W. and Ochs, K. (2015)
Frontiers in Immunology

Prostaglandin E2 and the EP receptors in malignancy: possible therapeutic targets?

O'Callaghan, G. and Houston, A. (2015)
British Journal of Pharmacology

Metabolic Reprogramming of Immune Cells in Cancer Progression

Biswas, S. (2015)

An endogenous tumour-promoting ligand of the human aryl hydrocarbon receptor

Opitz, C. A. et al. (2011)


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