The international American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) tumour-node-metastasis (TNM) staging system provides the current guidelines for the classification of cancer. However, among patients within the same stage, the clinical outcome can be very different. More recently, a novel definition of cancer has emerged, implicating at all stages a complex and dynamic interaction between tumour cells and the immune system. This has enabled the definition of the immune contexture, representing the pre-existing immune parameters associated with patient survival. Even so, the role of distinct immune cell types in modulating cancer progression is increasingly emerging. An immune-based assay named the ‘Immunoscore’ was defined to quantify the in situ T cell infiltrate and was demonstrated to be superior to the AJCC/UICC TNM classification for patients with colorectal cancer. This Review provides a broad overview of the main immune parameters positively or negatively shaping cancer development, including the Immunoscore, and their prognostic and predictive value. The importance of the immune system in cancer control is demonstrated by the requirement for a pre-existing intratumour adaptive immune response for effective immunotherapies, such as checkpoint inhibitors. Finally, we discuss how the combination of multiple immune parameters, rather than individual ones, might increase prognostic and/or predictive power.
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This work was supported by grants from the French National Cancer Institute (INCa), Cancéropôle Île de France, INSERM, AstraZeneca, the Transcan ERAnet European Project, La Ligue contre le Cancer, the Qatar National Research Fund, Cancer Research for Personalized Medicine (CARPEM), the Paris Alliance of Cancer Research Institutes and LabEx Immuno-oncology.
J.G. is a co-founder of HalioDx. H.K.A. is an employee of AstraZeneca. D.B. is now an employee of Roche Diagnostics International, but the work on this review was done when employed by INSERM.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
- Immune contexture
A concept that encompasses the combination of immune parameters linked with patients’ survival associating the type, density, immune functional orientation and localization of immune cells within a tumour. ‘Contexture’ refers to the act of assembling parts into a whole, and an arrangement of interconnected parts.
- CD3+ T cells
T cells can be distinguished from other lymphocytes by the presence of a T cell receptor and CD3 on the cell surface of all T cells.
- Humoral adaptive immunity
Immunity mediated by macromolecules found in extracellular fluids such as secreted antibodies, complement proteins and certain antimicrobial peptides and that involves the activation of B cells.
A cytoplasmic structure found in mast cells that functions as storage for preformed mediators, which are promptly released by exocytosis on stimulation.
- Neutrophil extracellular traps
(NETs). Networks of extracellular fibres, primarily composed of DNA from neutrophils, which bind pathogens.
- Effector memory T cells
Cells whose primary function is to augment an immune response when reactivated. These lymphocytes are primarily active as the CD8 variants, and thus are mainly responsible for cytotoxic actions against pathogens.
- CD8+ central memory T cells
Cells that are CD62LhiCCR7hi; CD62L and CCR7 facilitate homing of these cells to secondary lymphoid organs. They provide central immunosurveillance against known pathogens and can give rise to both effector and effector memory T cells following antigen re-encounter. They can also localize to peripheral tissues, where they participate in primary immunosurveillance.
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Bruni, D., Angell, H.K. & Galon, J. The immune contexture and Immunoscore in cancer prognosis and therapeutic efficacy. Nat Rev Cancer (2020). https://doi.org/10.1038/s41568-020-0285-7