De Henau, O. et al. Overcoming resistance to checkpoint blockade therapy by targeting PI3Kγ in myeloid cells. Nature 539, 443–447 (2016).
Kaneda, M. M. et al. PI3Kγ is a molecular switch that controls immune suppression. Nature 539, 437–442 (2016).
Quail, D. F. et al. The tumor microenvironment underlies acquired resistance to CSF-1R inhibition in gliomas. Science 352, aad3018 (2016).
Quail, D. F. & Joyce, J. A. Microenvironmental regulation of tumor progression and metastasis. Nat. Med. 19, 1423–1437 (2013).
Colegio, O. R. et al. Functional polarization of tumour-associated macrophages by tumour-derived lactic acid. Nature 513, 559–563 (2014).
Condeelis, J. & Pollard, J. W. Macrophages: obligate partners for tumor cell migration, invasion, and metastasis. Cell 124, 263–266 (2006).
Franklin, R. A. et al. The cellular and molecular origin of tumor-associated macrophages. Science 344, 921–925 (2014).
Junttila, M. R. & de Sauvage, F. J. Influence of tumour micro-environment heterogeneity on therapeutic response. Nature 501, 346–354 (2013).
Noy, R. & Pollard, J. W. Tumor-associated macrophages: from mechanisms to therapy. Immunity 41, 49–61 (2014).
Qian, B. Z. et al. CCL2 recruits inflammatory monocytes to facilitate breast-tumour metastasis. Nature 475, 222–225 (2011).
Qian, B. Z. & Pollard, J. W. Macrophage diversity enhances tumor progression and metastasis. Cell 141, 39–51 (2010).
Preusser, M., Lim, M., Hafler, D. A., Reardon, D. A. & Sampson, J. H. Prospects of immune checkpoint modulators in the treatment of glioblastoma. Nat. Rev. Neurol. 11, 504–514 (2015).
Sharma, P. & Allison, J. P. The future of immune checkpoint therapy. Science 348, 56–61 (2015).
Wen, P. Y. & Reardon, D. A. Neuro-oncology in 2015: progress in glioma diagnosis, classification and treatment. Nat. Rev. Neurol. 12, 69–70 (2016).
Hambardzumyan, D., Gutmann, D. H. & Kettenmann, H. The role of microglia and macrophages in glioma maintenance and progression. Nat. Neurosci. 19, 20–27 (2016).
Thomas, A. A. et al. Regulatory T cells are not a strong predictor of survival for patients with glioblastoma. Neuro Oncol. 17, 801–809 (2015).
Pyonteck, S. M. et al. CSF-1R inhibition alters macrophage polarization and blocks glioma progression. Nat. Med. 19, 1264–1272 (2013).
Gosselin, D. et al. Environment drives selection and function of enhancers controlling tissue-specific macrophage identities. Cell 159, 1327–1340 (2014).
Gabrilovich, D. I., Ostrand-Rosenberg, S. & Bronte, V. Coordinated regulation of myeloid cells by tumours. Nat. Rev. Immunol. 12, 253–268 (2012).
Gabriely, G., Wheeler, M. A., Takenaka, M. C. & Quintana, F. J. Role of AHR and HIF-1α in glioblastoma metabolism. Trends Endocrinol. Metab. 28, 428–436 (2017).
Opitz, C. A. et al. An endogenous tumour-promoting ligand of the human aryl hydrocarbon receptor. Nature 478, 197–203 (2011).
Gutiérrez-Vázquez, C. & Quintana, F. J. Regulation of the immune response by the aryl hydrocarbon receptor. Immunity 48, 19–33 (2018).
Mascanfroni, I. D. et al. Metabolic control of type 1 regulatory T cell differentiation by AHR and HIF1-α. Nat. Med. 21, 638–646 (2015).
Bessede, A. et al. Aryl hydrocarbon receptor control of a disease tolerance defence pathway. Nature 511, 184–190 (2014).
Rothhammer, V. et al. Microglial control of astrocytes in response to microbial metabolites. Nature 557, 724–728 (2018).
Mukthavaram, R. et al. Effect of the JAK2/STAT3 inhibitor SAR317461 on human glioblastoma tumorspheres. J. Transl Med. 13, 269 (2015).
Thota, B. et al. STAT-1 expression is regulated by IGFBP-3 in malignant glioma cells and is a strong predictor of poor survival in patients with glioblastoma. J. Neurosurg. 121, 374–383 (2014).
Rothhammer, V. et al. Type I interferons and microbial metabolites of tryptophan modulate astrocyte activity and central nervous system inflammation via the aryl hydrocarbon receptor. Nat. Med. 22, 586–597 (2016).
Brennan, C. W. et al. The somatic genomic landscape of glioblastoma. Cell 155, 462–477 (2013).
The Cancer Genome Atlas Research Network. Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature 455, 1061–1068 (2008).
Bowman, R. L. et al. Macrophage ontogeny underlies differences in tumor-specific education in brain malignancies. Cell Rep. 17, 2445–2459 (2016).
Platten, M. et al. Monocyte chemoattractant protein-1 increases microglial infiltration and aggressiveness of gliomas. Ann. Neurol. 54, 388–392 (2003).
Mayo, L. et al. Regulation of astrocyte activation by glycolipids drives chronic CNS inflammation. Nat. Med. 20, 1147–1156 (2014).
Phillips, R. J., Lutz, M. & Premack, B. Differential signaling mechanisms regulate expression of CC chemokine receptor-2 during monocyte maturation. J. Inflamm. (Lond.) 2, 14 (2005).
Sozzani, S. et al. MCP-1 and CCR2 in HIV infection: regulation of agonist and receptor expression. J. Leukoc. Biol. 62, 30–33 (1997).
Platten, M. et al. Treatment of autoimmune neuroinflammation with a synthetic tryptophan metabolite. Science 310, 850–855 (2005).
Liao, X. et al. Krüppel-like factor 4 regulates macrophage polarization. J. Clin. Invest. 121, 2736–2749 (2011).
Yeste, A. et al. Tolerogenic nanoparticles inhibit T cell-mediated autoimmunity through SOCS2. Sci. Signal. 9, ra61 (2016).
Takenaka, M. C., Robson, S. & Quintana, F. J. Regulation of the T cell response by CD39. Trends Immunol. 37, 427–439 (2016).
Deaglio, S. et al. Adenosine generation catalyzed by CD39 and CD73 expressed on regulatory T cells mediates immune suppression. J. Exp. Med. 204, 1257–1265 (2007).
Singer, M. et al. A distinct gene module for dysfunction uncoupled from activation in tumor-infiltrating T Cells. Cell 166, 1500–1511.e9 (2016).
Wherry, E. J. & Kurachi, M. Molecular and cellular insights into T cell exhaustion. Nat. Rev. Immunol. 15, 486–499 (2015).
Verhaak, R. G. et al. Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell 17, 98–110 (2010).
Nirschl, C. J. et al. IFNγ-dependent tissue-immune homeostasis is co-opted in the tumor microenvironment. Cell 170, 127–141 (2017).
Wang, Q. et al. Tumor evolution of glioma-intrinsic gene expression subtypes associates with immunological changes in the microenvironment. Cancer Cell 32, 42–56.e6 (2017).
Wherry, E. J. T cell exhaustion. Nat. Immunol. 12, 492–499 (2011).
Kohanbash, G. et al. Isocitrate dehydrogenase mutations suppress STAT1 and CD8+ T cell accumulation in gliomas. J. Clin. Invest. 127, 1425–1437 (2017).
Thaiss, C. A., Zmora, N., Levy, M. & Elinav, E. The microbiome and innate immunity. Nature 535, 65–74 (2016).
Vétizou, M. et al. Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota. Science 350, 1079–1084 (2015).
Okey, A. B., Vella, L. M. & Harper, P. A. Detection and characterization of a low affinity form of cytosolic Ah receptor in livers of mice nonresponsive to induction of cytochrome P1-450 by 3-methylcholanthrene. Mol. Pharmacol. 35, 823–830 (1989).
Gabriely, G. et al. Targeting latency-associated peptide promotes antitumor immunity. Sci. Immunol. 2, 2 (2017).
Bennett, M. L. et al. New tools for studying microglia in the mouse and human CNS. Proc. Natl Acad. Sci. USA 113, E1738–E1746 (2016).
Durafourt, B. A., Moore, C. S., Blain, M. & Antel, J. P. Isolating, culturing, and polarizing primary human adult and fetal microglia. Methods Mol. Biol. 1041, 199–211 (2013).
David, B. A. et al. Isolation and high-dimensional phenotyping of gastrointestinal immune cells. Immunology 151, 56–70 (2017).
Mascanfroni, I. D. et al. IL-27 acts on DCs to suppress the T cell response and autoimmunity by inducing expression of the immunoregulatory molecule CD39. Nat. Immunol. 14, 1054–1063 (2013).
Shin, S. et al. NRF2 modulates aryl hydrocarbon receptor signaling: influence on adipogenesis. Mol. Cell. Biol. 27, 7188–7197 (2007).
Karpurapu, M. et al. Krüppel like factor 4 promoter undergoes active demethylation during monocyte/macrophage differentiation. PLoS One 9, e93362 (2014).