Cancer immune contexture and immunotherapy

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Highlights

  • The immune contexture is a powerful tool to predict patient's prognosis.

  • The prognostic impact of TILs is modulated by other stromal components.

  • The immune contexture and its prognostic impact is reproduced in metastases.

  • Carcinogenesis pathways influence the immune contexture and its impact.

  • Classification in three immune subgroups and may guide immunotherapies.

The immune contexture that characterizes the density, the location, the organization and the functional orientation of tumor-infiltrating immune cells in cancers has a clinical impact on patient's outcome. It is, in great part, shaped by the malignant cells, as in a given cancer type, tumors presenting different oncogenic processes have different immune contextures. Moreover, the immune contexture in metastatic sites reflects that of the corresponding primary tumors. Finally, the components forming the immune contexture represent targets and markers of efficient anti-cancer immunotherapies.

Introduction

Cancers grow and spread in tissues where the malignant cells interact with blood and lymphatic vessels, stromal cells and hematopoietic cells involved in immune and inflammatory reactions. This landscape constitutes the immune contexture of a tumor which is of paramount importance for patients’ clinical outcome, is predictive of responses to therapies and helps identifying novel targets for immunotherapies [1].

Section snippets

Clinical impact of the immune contexture in different primary tumors

The immune contexture is a concept that emerged from studies mostly performed in human colorectal cancer (CRC). A comprehensive analysis of a large collection of primary CRC tumors revealed that a high density of intratumoral memory T cells correlates with patients’ longer disease-free (DFS) and overall (OS) survivals [2], confirming a previous report in ovarian cancer [3]. A closer histopathological analysis of CRC tumors highlighted the fact that the T cells were not stochastically

Clinical impact of the immune contexture in metastatic sites

It is intuitively thought that tumor progression is accompanied by tumor escape from the immune system [28]. If this escape linearly followed cancer progression, the immune contexture of metastatic sites should not impact clinical outcome. However, high densities of CD8+ T cells in hepatic and lung metastases of CRC correlate with longer OS [25], as in primary CRC [4••]. Densities of infiltrating immune cells were shown to be correlated between the primary tumors and matched metastases [25].

Clinical impact of the immune contexture within a given cancer

Whole genome transcriptomic analyses provide a novel way to classify subgroups in a given cancer type. These unsupervised approaches complement genomic classifications by identifying malignant cell subgroups with distinct functional traits. We undertook an analysis of the expression of immune genes and the concomitant immune cell infiltration in cohorts of various human cancers. To precisely analyze the immune contexture of large collections of human cancers, we established transcriptomic

The immune contexture and response to therapy

The immune microenvironment of tumors not only reflects the oncogenic processes of a cancer in a patient, but is also a constitutive arm of cancer control and thus of patient's clinical outcome. It is therefore likely that therapeutic interventions modifying the immune contexture will result in profound changes in cancer evolution. Characterizing the immune contexture or the corresponding molecular profile of a tumor in a patient will allow clinicians to propose the most appropriate therapies.

Financial support

This work was supported by the ‘Institut National de la Santé et de la Recherche Médicale’, the University Paris-Descartes, the University Pierre et Marie Curie, the Institut National du Cancer (2009-1-PLBIO-07-INSERM 6-1, 2010-1-PLBIO-03-INSERM 6-1, 2011-1-PLBIO-06-INSERM 6-1), CARPEM (CAncer Research for PErsonalized Medicine), Labex Immuno-Oncology (LAXE62_9UMS872 FRIDMAN, 11LAXE62_9UMS872 FRIDMAN), and the Fondation ARC pour la Rercherche sur le Cancer (SL220110603483), the Universidad de

References and recommended reading

Papers of particular interest, published within the period of review, have been highlighted as:

  • • of special interest

  • •• of outstanding interest

Acknowledgements

We thank the members of the teams of I. Cremer/J.L. Teillaud and J. Galon at the Cordeliers Research Center for their fruitful discussions and who performed most of the work cited in this review.

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    These authors contributed equally to this work.

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