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Innate and adaptive immune cells in the tumor microenvironment

Abstract

Most tumor cells express antigens that can mediate recognition by host CD8+ T cells. Cancers that are detected clinically must have evaded antitumor immune responses to grow progressively. Recent work has suggested two broad categories of tumor escape based on cellular and molecular characteristics of the tumor microenvironment. One major subset shows a T cell–inflamed phenotype consisting of infiltrating T cells, a broad chemokine profile and a type I interferon signature indicative of innate immune activation. These tumors appear to resist immune attack through the dominant inhibitory effects of immune system–suppressive pathways. The other major phenotype lacks this T cell–inflamed phenotype and appears to resist immune attack through immune system exclusion or ignorance. These two major phenotypes of tumor microenvironment may require distinct immunotherapeutic interventions for maximal therapeutic effect.

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Figure 1: Working model for the segregation of tumors based on immune system regulatory pathways in the tumor microenvironment.

Marina Corral Spence

Figure 2: Therapeutic interventions being investigated that target immune inhibitory pathways in the tumor microenvironment.

Marina Corral Spence

Figure 3: Therapeutic strategies being considered that may promote appropriate inflammation and/or innate immune activation in the tumor microenvironment.

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Gajewski, T., Schreiber, H. & Fu, YX. Innate and adaptive immune cells in the tumor microenvironment. Nat Immunol 14, 1014–1022 (2013). https://doi.org/10.1038/ni.2703

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