Tryptophan-derived microbial metabolites activate the aryl hydrocarbon receptor in tumor-associated macrophages to suppress anti-tumor immunity

• Published in: Immunity (Cambridge, Mass.) Vol. 55; no. 2; pp. 324 - 340.e8
• Main Authors: Hezaveh, Kebria, Shinde, Rahul S, Klötgen, Andreas, Halaby, Marie Jo, Lamorte, Sara, Ciudad, M. Teresa, Quevedo, Rene, Neufeld, Luke, Liu, Zhe Qi, Jin, Robbie, Grünwald, Barbara T, Foerster, Elisabeth G, Chaharlangi, Danica, Guo, Mengdi, Makhijani, Priya, Zhang, Xin, Pugh, Trevor J, Pinto, Devanand M, Co, Ileana L, McGuigan, Alison P, Jang, Gun Ho, Khokha, Rama, Ohashi, Pamela S, O’Kane, Grainne M, Gallinger, Steven, Navarre, William W, Maughan, Heather, Philpott, Dana J, Brooks, David G, McGaha, Tracy L
• Format: Journal Article
• Language: English
• Published: United States Elsevier 08.02.2022
• Subjects: Animals; aryl hydrocarbon receptor; Carcinoma, Pancreatic Ductal - immunology; Carcinoma, Pancreatic Ductal - metabolism; Carcinoma, Pancreatic Ductal - mortality; Carcinoma, Pancreatic Ductal - pathology; CD8-Positive T-Lymphocytes - immunology; Humans; immune suppression; Immune Tolerance - immunology; immunotherapy; indoles; Indoles - immunology; Indoles - metabolism; Lymphocytes, Tumor-Infiltrating - immunology; macrophage; metabolism; Mice; microbiome; Microbiota - immunology; pancreatic cancer; Pancreatic Neoplasms - immunology; Pancreatic Neoplasms - metabolism; Pancreatic Neoplasms - mortality; Pancreatic Neoplasms - pathology; Prognosis; Receptors, Aryl Hydrocarbon - antagonists & inhibitors; Receptors, Aryl Hydrocarbon - genetics; Receptors, Aryl Hydrocarbon - immunology; Receptors, Aryl Hydrocarbon - metabolism; T cells; Tryptophan - immunology; Tryptophan - metabolism; tumor microenvironment; Tumor Microenvironment - drug effects; Tumor Microenvironment - immunology; Tumor-Associated Macrophages - immunology; Tumor-Associated Macrophages - metabolism; indoles; pancreatic cancer; immunotherapy; macrophage; metabolism; tumor microenvironment; T cells; immune suppression; microbiome; aryl hydrocarbon receptor

The aryl hydrocarbon receptor (AhR) is a sensor of products of tryptophan metabolism and a potent modulator of immunity. Here, we examined the impact of AhR in tumor-associated macrophage (TAM) function in pancreatic ductal adenocarcinoma (PDAC). TAMs exhibited high AhR activity and Ahr-deficient ma...