Towards the introduction of the 'Immunoscore' in the classification of malignant tumours

Jérôme Galon, Bernhard Mlecnik, Gabriela Bindea, Helen K Angell, Anne Berger, Christine Lagorce, Alessandro Lugli, Inti Zlobec, Arndt Hartmann, Carlo Bifulco, Iris D Nagtegaal, Richard Palmqvist, Giuseppe V Masucci, Gerardo Botti, Fabiana Tatangelo, Paolo Delrio, Michele Maio, Luigi Laghi, Fabio Grizzi, Martin Asslaber, Corrado D'Arrigo, Fernando Vidal-Vanaclocha, Eva Zavadova, Lotfi Chouchane, Pamela S Ohashi, Sara Hafezi-Bakhtiari, Bradly G Wouters, Michael Roehrl, Linh Nguyen, Yutaka Kawakami, Shoichi Hazama, Kiyotaka Okuno, Shuji Ogino, Peter Gibbs, Paul Waring, Noriyuki Sato, Toshihiko Torigoe, Kyogo Itoh, Prabhu S Patel, Shilin N Shukla, Yili Wang, Scott Kopetz, Frank A Sinicrope, Viorel Scripcariu, Paolo A Ascierto, Francesco M Marincola, Bernard A Fox, Franck Pagès, Jérôme Galon, Bernhard Mlecnik, Gabriela Bindea, Helen K Angell, Anne Berger, Christine Lagorce, Alessandro Lugli, Inti Zlobec, Arndt Hartmann, Carlo Bifulco, Iris D Nagtegaal, Richard Palmqvist, Giuseppe V Masucci, Gerardo Botti, Fabiana Tatangelo, Paolo Delrio, Michele Maio, Luigi Laghi, Fabio Grizzi, Martin Asslaber, Corrado D'Arrigo, Fernando Vidal-Vanaclocha, Eva Zavadova, Lotfi Chouchane, Pamela S Ohashi, Sara Hafezi-Bakhtiari, Bradly G Wouters, Michael Roehrl, Linh Nguyen, Yutaka Kawakami, Shoichi Hazama, Kiyotaka Okuno, Shuji Ogino, Peter Gibbs, Paul Waring, Noriyuki Sato, Toshihiko Torigoe, Kyogo Itoh, Prabhu S Patel, Shilin N Shukla, Yili Wang, Scott Kopetz, Frank A Sinicrope, Viorel Scripcariu, Paolo A Ascierto, Francesco M Marincola, Bernard A Fox, Franck Pagès

Abstract

The American Joint Committee on Cancer/Union Internationale Contre le Cancer (AJCC/UICC) TNM staging system provides the most reliable guidelines for the routine prognostication and treatment of colorectal carcinoma. This traditional tumour staging summarizes data on tumour burden (T), the presence of cancer cells in draining and regional lymph nodes (N) and evidence for distant metastases (M). However, it is now recognized that the clinical outcome can vary significantly among patients within the same stage. The current classification provides limited prognostic information and does not predict response to therapy. Multiple ways to classify cancer and to distinguish different subtypes of colorectal cancer have been proposed, including morphology, cell origin, molecular pathways, mutation status and gene expression-based stratification. These parameters rely on tumour-cell characteristics. Extensive literature has investigated the host immune response against cancer and demonstrated the prognostic impact of the in situ immune cell infiltrate in tumours. A methodology named 'Immunoscore' has been defined to quantify the in situ immune infiltrate. In colorectal cancer, the Immunoscore may add to the significance of the current AJCC/UICC TNM classification, since it has been demonstrated to be a prognostic factor superior to the AJCC/UICC TNM classification. An international consortium has been initiated to validate and promote the Immunoscore in routine clinical settings. The results of this international consortium may result in the implementation of the Immunoscore as a new component for the classification of cancer, designated TNM-I (TNM-Immune).

Keywords: Immunoscore; T cells; classification; colon carcinoma; colorectal cancer; immune response; predictive markers; prognostic markers; tumour microenvironment.

© 2013 The Authors. Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Figures

Figure 1
Figure 1
Classification of colorectal cancer. (Top) Classification based on tumour cell extension and invasion. (Middle) Classification based on tumour cell characteristics. Adeno NOS, adenocarcinoma not otherwise specified; Transit-amplifying-R, transit-amplifying-resistant; Transit-amplifying-S, transit-amplifying-Sensitive; CIN, chromosomal unstable; MSI, microsatellite unstable; CIMP, CpG island methylator phenotype. (Bottom) Classification based on the host immune response using the Immunoscore.
Figure 2
Figure 2
(Top) Immunoscore definition and methodology. (Bottom) Immunohistochemistry of a colorectal tumour stained for CD3+ T cells (brown).
Figure 3
Figure 3
Correspondence between the immune contexture and the Immunoscore.
Figure 4
Figure 4
Schematic representation of cancer classification based on tumour-microenvironment-related parameters (Immunoscore), based on tumour extension and invasion (T, N, M stages), and based on five alternative tumour-related methods.
Figure 5
Figure 5
Characteristics of a good biomarker and of the Immunoscore.

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