Cancer is a complex disease whose outcome depends largely on the cross-talk between the tumor and its microenvironment. Here, we review the evolution of the field of tumor immunology and the ...advances, in lockstep, of our understanding of cancer as a disease. We discuss the involvement of different immune cells at distinct stages of tumor progression and how immune contexture determinants shaping tumor development are being exploited therapeutically. Current clinical stratification schemes focus on the tumor histopathology and the molecular characteristics of the tumor cell. We argue for the importance of revising these stratification systems to include immune parameters so as to address the immediate need for improved prognostic and/or predictive information to guide clinical decisions.
Galon and Bruni review the evolution of the field of tumor immunology and discuss how these advances have shaped our understanding of cancer as a disease. They discuss current cancer stratification systems and argue for the importance of revising these to include immune parameters so as to better guide clinical decisions.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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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FZAB, GEOZS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The CluePedia Cytoscape plugin is a search tool for new markers potentially associated to pathways. CluePedia calculates linear and non-linear statistical dependencies from experimental data. Genes, ...proteins and miRNAs can be connected based on in silico and/or experimental information and integrated into a ClueGO network of terms/pathways. Interrelations within each pathway can be investigated, and new potential associations may be revealed through gene/protein/miRNA enrichments. A pathway-like visualization can be created using the Cerebral plugin layout. Combining all these features is essential for data interpretation and the generation of new hypotheses. The CluePedia Cytoscape plugin is user-friendly and has an expressive and intuitive visualization.
http://www.ici.upmc.fr/cluepedia/ and via the Cytoscape plugin manager. The user manual is available at the CluePedia website.
Highlights • We first define the immune contexture. • The relevance of the Immunoscore as a prognostic marker is examined. • Additional prognostic and predictive markers are discussed. • The overlap ...between prognostic and predictive markers is described. • The link between tumor response to therapy and the immune reaction is highlighted.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Current cancer classification is based on intrinsic tumor parameters such as characteristic of tumor cells, tumor progression, tumor invasion and the presence of distant metastases, as summarized by ...the AJCC/UICC-TNM stratification system. There is currently no immune-based classification of cancer. We provided evidence that the immune contexture, as defined by the type, density, functional immune orientation and the location of immune cells within tumor, strongly influences the outcome of colorectal cancer (CRC) patients. To translate this information to the clinic, we developed an immunohistochemistry and digital pathology-based assay named Immunoscore that allows the quantification of two T cell subsets (CD3 and CD8) in two tumor regions (core and invasive margin of tumors). We have demonstrated that the standardized consensus Immunoscore has a prognostic value superior and independent to the one of the traditional TNM system in an international study in stage I-III colon cancer patients, therefore validating the Immunoscore as the first immune-based scoring system. In additional analyses, we showed the prognostic value of Immunoscore for stage II-IV CRC patients, as well as the predictive value of Immunoscore in stage III colon cancer patients. The Immunoscore may help predict and stratify patients who will benefit from adjuvant chemotherapy. Moreover, the Immunoscore allows the classification of tumors from hot to cold categories, and could consequently guide clinical decision for the choice of treatment.
The Immunoscore: Colon Cancer and Beyond Angell, Helen K; Bruni, Daniela; Barrett, J Carl ...
Clinical cancer research,
2020-Jan-15, 2020-01-15, 20200115, Volume:
26, Issue:
2
Journal Article
Peer reviewed
Tumors evolve in close interaction with their microenvironment, which encompasses a continual tension between the developing tumor and the host immune system. Clinical trials have shown that ...appropriate enhancement of a tumor immune response can lead to long-lasting clinical responses and patient benefit. Understanding the contribution of the immune contexture, in addition to the molecular subtype across different tumor indications, is a significant knowledge gap with limited sagacity to drive rational immunotherapy combinations. To better inform clinical studies, we must first strive to understand the multifaceted elements of the tumor-immune interaction, the spatiotemporal interplay of numerous different immune cell types, in conjunction with an understanding of the oncogenic drivers and mutations that may lead to presentation of neoepitopes and could drive changes within the tumor microenvironment. In this review, we discuss the Immunoscore and its probable universal characteristic. The overlay of immune quantification with the molecular segments of disease and how this may benefit identification of patients at high risk of tumor recurrence will be discussed. The Immunoscore may translate to provide a tumor agnostic method to define immune fitness of a given tumor and predict and stratify patients who will benefit from certain therapies (in particular immune therapies) and, ultimately, help save the lives of patients with cancer.
Colorectal cancer is one of the most common malignancies, often presenting with a poor prognosis. To date, the anatomic extent of disease has been by far the most important prognostic factor. ...Recently, we obtained evidence that the type, density, and location of immune cells in colorectal cancer could provide a prognostic factor superior and independent to that of criteria related to the anatomic extent of the tumor. Here, we discuss the meaning and potential implications of this novel finding.
The role of the adaptive immune response in controlling the growth and recurrence of human tumors has been controversial. We characterized the tumor-infiltrating immune cells in large cohorts of ...human colorectal cancers by gene expression profiling and in situ immunohistochemical staining. Collectively, the immunological data (the type, density, and location of immune cells within the tumor samples) were found to be a better predictor of patient survival than the histopathological methods currently used to stage colorectal cancer. The results were validated in two additional patient populations. These data support the hypothesis that the adaptive immune response influences the behavior of human tumors. In situ analysis of tumor-infiltrating immune cells may therefore be a valuable prognostic tool in the treatment of colorectal cancer and possibly other malignancies.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
We have developed ClueGO, an easy to use Cytoscape plug-in that strongly improves biological interpretation of large lists of genes. ClueGO integrates Gene Ontology (GO) terms as well as ...KEGG/BioCarta pathways and creates a functionally organized GO/pathway term network. It can analyze one or compare two lists of genes and comprehensively visualizes functionally grouped terms. A one-click update option allows ClueGO to automatically download the most recent GO/KEGG release at any time. ClueGO provides an intuitive representation of the analysis results and can be optionally used in conjunction with the GOlorize plug-in. Availability: http://www.ici.upmc.fr/cluego/cluegoDownload.shtml Contact: jerome.galon@crc.jussieu.fr Supplementary information: Supplementary data are available at Bioinformatics online.
Abstract
Summary
Large scale technologies produce massive amounts of experimental data that need to be investigated. To improve their biological interpretation we have developed ClueGO, a Cytoscape ...App that selects representative Gene Onology terms and pathways for one or multiple lists of genes/proteins and visualizes them into functionally organized networks. Because of its reliability, userfriendliness and support of many species ClueGO gained a large community of users. To further allow scientists programmatic access to ClueGO with R, Python, JavaScript etc., we implemented the cyREST API into ClueGO. In this article we describe this novel, complementary way of accessing ClueGO via REST, and provide R and Phyton examples to demonstrate how ClueGO workflows can be integrated into bioinformatic analysis pipelines.
Availability and implementation
ClueGO is available in the Cytoscape App Store (http://apps.cytoscape.org/apps/cluego).
Supplementary information
Supplementary data are available at Bioinformatics online.
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