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The immune contexture in human tumours: impact on clinical outcome

Abstract

Tumours grow within an intricate network of epithelial cells, vascular and lymphatic vessels, cytokines and chemokines, and infiltrating immune cells. Different types of infiltrating immune cells have different effects on tumour progression, which can vary according to cancer type. In this Opinion article we discuss how the context-specific nature of infiltrating immune cells can affect the prognosis of patients.

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Figure 1: The immune contexture.
Figure 2: The association of immune cell infiltrates with prognosis in various types of cancer.
Figure 3: Cells and chemokines that coordinate the tumour microenvironment.

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Acknowledgements

This work was supported by grants from the National Cancer Institute (INCa) (grants 07/3D1616, PLBio2009-07 and PLBio2010), the Canceropole Ile de France (grant R09194DD), Ville de Paris, the Association pour la Recherche sur le Cancer (ARC) (grants PEMT, 07/3D1616 and 3,185), ARC, Fondation de France, INSERM, Université Pierre et Marie Curie, Université Paris Descartes, Qatar-Foundation NPRP (grant 09-1174-3-291), the European Commission (7FP, Geninca Consortium, grant 202,230) and the LabEx Immuno-Oncology. The authors thank M. C. Dieu-Nosjean, I. Cremer, D. Damotte, E. Tartour, J. L. Teillaud, as well as the other members of Immune Microenvironment and Tumours and Integrative Cancer Immunology teams of the Cordeliers Reseach Centre for their invaluable contribution. The authors thank T. Fredriksen for helping with the drawing of the figures.

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Glossary

Cytotoxic T cells

CD3+CD8+ effector T cells with cytotoxic granules that contain perforin and granzymes, which are released on interaction with target cells expressing cognate antigen. This leads to the death of target cells by apoptosis.

Dendritic cells

Cells that capture microorganisms or dead tumour cells and that process them to present antigen to T cells in secondary or tertiary lymphoid organs. They express high levels of co-stimulatory molecules, which allows them to activate naive T cells.

High endothelial venules

Specialized venules that occur in secondary lymphoid organs, except the spleen. They allow continuous transmigration of lymphocytes as a consequence of the constitutive expression of adhesion molecules and chemokines at their luminal surface.

Macrophages

Can be subdivided according to their cellular properties and cytokine secretion profiles. M1 macrophages secrete pro-inflammatory cytokines (IL-1, IL-6 and TNF), release reactive oxygen and reactive nitrate species and have a pro-inflammatory role. M2 macrophages secrete IL-4, IL-10, IL-13 and TGFβ and have an anti-inflammatory role, promote angiogenesis and favour tumour progression.

Memory T cells

CD3+CD4+CD45RO+ and CD3+CD8+CD45RO+ cells that have encountered antigen and that respond faster and with increased intensity on antigenic stimulation compared with naive T cells.

Myeloid-derived suppressor cells

(MDSCs). Heterogeneous population of polymorphonuclear and monocytic CD11b+GR1+ cells that inhibit T cell activation.

Naive T cells

CD3+CD4+ and CD3+CD8+ cells that differentiate into effector T cells (CD4+ T helper cells or CD8+ cytotoxic T cells) in secondary lymphoid organs or TLS after stimulation with three signals: antigen, co-stimulatory molecules and cytokines.

Regulatory T (TReg) cells

Population of CD3+CD4+ T cells that inhibit effector B and T cells. Some produce cytokines with immunosuppressive activities; for example, IL-10 and TGFβ. They have a central role in suppressing anti-self immune responses to prevent autoimmune diseases.

Tertiary lymphoid structures

(TLS). Ectopic lymphoid aggregates that are generated during the process of chronic immune stimulation and that exhibit the structural characteristics of secondary lymphoid organs.

T helper cells

Populations of CD3+CD4+ effector T cells that secrete cytokines with differential activities. TH1 cells produce IL-2 and IFNγ and favour cellular immunity (acting on CD8+ cytotoxic T cells, NK cells and macrophages). TH2 cells produce IL-4, IL-5 and IL-13 and favour humoral immunity (acting on B cells). TH17 cells produce IL-17A, IL-17F, IL-21 and IL-22 and favour anti-microbial tissue inflammation (acting on epithelial and endothelial cells, fibroblasts and immune cells).

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Fridman, W., Pagès, F., Sautès-Fridman, C. et al. The immune contexture in human tumours: impact on clinical outcome. Nat Rev Cancer 12, 298–306 (2012). https://doi.org/10.1038/nrc3245

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