From the immune contexture to the Immunoscore: the role of prognostic and predictive immune markers in cancer

Angell, Helen K.; Galon, Jérôme

doi:10.1016/j.coi.2013.03.004

Cited by 473 publications

(399 citation statements)

References 72 publications

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“…Récemment, des progrès importants ont été réalisés dans la perception du pronostic par l'analyse de la composante immunitaire du microenvironnement tumoral (Figure 1). Les tumeurs solides humaines présentent un infiltrat polymorphe et variable d'un patient à l'autre, composé de macrophages, de cellules dendritiques (DC), de polymorphonucléaires, de cellules NK (natural killer) et de cellules de l'immunité adaptative, et des lymphocytes B et T. Il a été montré dans de nombreuses tumeurs solides colorectales [7,9,20], dans des mélanomes, et dans des cancers de l'ovaire, de la tête et le cou, de la vessie, du sein, du foie, de la prostate, de la vessie et du poumon [6], qu'une forte infiltration lymphocytaire était associée à une survie prolongée. La majorité des études ont révélé qu'une forte infiltration intratumorale en lymphocytes T CD3 + , T CD8 + cytotoxiques et en lymphocytes T CD45RO + mémoires était corrélée à une survie sans récidive prolongée et un accroissement de la survie globale [7].…”

Section: Signatures Immunitaires Pronostiques Dans Différents Types Dunclassified

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Microenvironnement immunitaire et cancer

et al. 2014

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Section: Signatures Immunitaires Pronostiques Dans Différents Types Dunclassified

“…Cependant, ils ne prédisent en rien la sensibilité de la tumeur à un traitement donné, un rôle qui concerne les biomarqueurs prédictifs de réponse [20]. Dans la pratique, il est fréquent que plusieurs options thérapeutiques soient possibles, telles que des chimiothérapies ou des thérapies ciblées.…”

Section: Marqueurs Prédictifs De L'efficacité Thérapeutiqueunclassified

Microenvironnement immunitaire et cancer

et al. 2014

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“…5 Furthermore, transcriptomic analysis is capable of revealing 'multi-gene expression patterns' or 'metagenes' (i.e., aggregate patterns of gene expressions like a cluster of genes, exhibiting or stratified to exhibit collective high expression) as prognostic biomarkers. [10][11][12][13] Interestingly, recent progress in the fields of prognostic metagene biology in cancer has suggested that initial consensus-metagenes identified through biomarker discovery approaches may subsequently exhibit the ability to act as 'attractor'-metagenes for a further set of 'convergent'-metagenes.…”

Section: Introductionmentioning

confidence: 99%

“…Ideally, biomarkers should reflect the complexity of a tumor mass across various cancer-types. 5 Several clinical and pathological indicators have been introduced for estimating patient prognosis 6,7 however, while such systems are valuable, they mostly rely on clinical parameters or cancer cell-related factors. 6 The recently emerging role of the cancer cell-immune cell interface in shaping tumorigenesis [2][3][4] and the appearance of anticancer immunotherapy 8,9 has increased the need to identify new integrated as well as broad sets of prognostic biomarkers based on the cancer cell-immune cell interface.…”

Section: Introductionmentioning

confidence: 99%

Immunological metagene signatures derived from immunogenic cancer cell death associate with improved survival of patients with lung, breast or ovarian malignancies: A large-scale meta-analysis

2015

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The emerging role of the cancer cell-immune cell interface in shaping tumorigenesis/anticancer immunotherapy has increased the need to identify prognostic biomarkers. Henceforth, our primary aim was to identify the immunogenic cell death (ICD)-derived metagene signatures in breast, lung and ovarian cancer that associate with improved patient survival. To this end, we analyzed the prognostic impact of differential gene-expression of 33 pre-clinically-validated ICD-parameters through a large-scale metaanalysis involving 3,983 patients ('discovery' dataset) across lung (1,432), breast (1,115) and ovarian (1,436) malignancies. The main results were also substantiated in 'validation' datasets consisting of 818 patients of same cancer-types (i.e. 285 breast/274 lung/259 ovarian). The ICD-associated parameters exhibited a highly-clustered and largely cancer type-specific prognostic impact. Interestingly, we delineated ICDderived consensus-metagene signatures that exhibited a positive prognostic impact that was either cancer type-independent or specific. Importantly, most of these ICD-derived consensus-metagenes (acted as attractor-metagenes and thereby) 'attracted' highly co-expressing sets of genes or convergentmetagenes. These convergent-metagenes also exhibited positive prognostic impact in respective cancer types. Remarkably, we found that the cancer type-independent consensus-metagene acted as an 'attractor' for cancer-specific convergent-metagenes. This reaffirms that the immunological prognostic landscape of cancer tends to segregate between cancer-independent and cancer-type specific gene signatures. Moreover, this prognostic landscape was largely dominated by the classical T cell activity/ infiltration/function-related biomarkers. Interestingly, each cancer type tended to associate with biomarkers representing a specific T cell activity or function rather than pan-T cell biomarkers. Thus, our analysis confirms that ICD can serve as a platform for discovery of novel prognostic metagenes.

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“…With increased recognition of the importance of the immune system on the disease course of cancers, 31-36 approaches to study the mounting anti-cancer immunity in the absence of accessible autologous tumor tissue for read-out purposes are limited. It is crucial to find better ways to monitor the magnitude, and ideally the broadness, of therapy-generated T cell immune responses.…”

Section: Discussionmentioning

confidence: 99%

Autophagosome-based strategy to monitor apparent tumor-specific CD8 T cells in patients with prostate cancer

Ven

Hilton

Hu³

et al. 2018

OncoImmunology

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The immune system plays an essential role in eradicating cancer in concert with various treatment modalities. In the absence of autologous tumor material, no standardized method exists to assess T cell responses against the many antigens that may serve as cancer rejection antigens. Thus, development of methods to screen for therapy-induced anti-tumor responses is a high priority that could help tailor therapy. Here we tested whether a tumor-derived antigen source called DRibbles®, which contain a pool of defective ribosomal products (DRiPs), long-lived and short-lived proteins (SLiPs) and danger-associated molecular patterns (DAMPs), can be used to identify tumor-associated antigen (TAA)-specific responses in patients before or after immunotherapy treatment. Protein content, gene expression and non-synonymous – single nucleotide variants (ns-SNVs) present in UbiLT3 DRibbles were compared with prostate adenocarcinomas and the prostate GVAX vaccine cell lines (PC3/LNCaP). UbiLT3 DRibbles were found to share proteins, as well as match tumor sequences for ns-SNVs with prostate adenocarcinomas and with the cell lines PC3 and LNCaP. UbiLT3 DRibbles were used to monitor anti-tumor responses in patients vaccinated with allogeneic prostate GVAX. UbiLT3-DRibble-reactive CD8+ T-cell responses were detected in post-vaccine PBMC of 6/12 patients (range 0.85–22% of CD8+ cells) after 1 week in vitro stimulation (p = 0.007 vs. pre-vaccine). In conclusion, a cancer-derived autophagosome-enriched preparation, packaging over 100 proteins over-expressed in prostate cancer into microvesicles containing DAMPs, could be used to identify CD8+ T cells in peripheral blood from patients after prostate GVAX vaccination and may represent a general method to monitor anti-cancer T cell responses following immunotherapy.

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From the immune contexture to the Immunoscore: the role of prognostic and predictive immune markers in cancer

Cited by 473 publications

References 72 publications

Microenvironnement immunitaire et cancer

Microenvironnement immunitaire et cancer

Immunological metagene signatures derived from immunogenic cancer cell death associate with improved survival of patients with lung, breast or ovarian malignancies: A large-scale meta-analysis

Autophagosome-based strategy to monitor apparent tumor-specific CD8 T cells in patients with prostate cancer

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