Title

International validation of the consensus Immunoscore for the classification of colon cancer: a prognostic and accuracy study.

Authors

Franck Pagès
Bernhard Mlecnik
Florence Marliot
Gabriela Bindea
Fang-Shu Ou
Carlo Bifulco, Department of Pathology, Providence Portland Medical Center, Portland, OR, USA.
Alessandro Lugli
Inti Zlobec
Tilman T Rau
Martin D Berger
Iris D Nagtegaal
Elisa Vink-Börger
Arndt Hartmann
Carol Geppert
Julie Kolwelter
Susanne Merkel
Robert Grützmann
Marc Van den Eynde
Anne Jouret-Mourin
Alex Kartheuser
Daniel Léonard
Christophe Remue
Julia Y Wang
Prashant Bavi
Michael H A Roehrl
Pamela S Ohashi
Linh T Nguyen
SeongJun Han
Heather L MacGregor
Sara Hafezi-Bakhtiari
Bradly G Wouters
Giuseppe V Masucci
Emilia K Andersson
Eva Zavadova
Michal Vocka
Jan Spacek
Lubos Petruzelka
Bohuslav Konopasek
Pavel Dundr
Helena Skalova
Kristyna Nemejcova
Gerardo Botti
Fabiana Tatangelo
Paolo Delrio
Gennaro Ciliberto
Michele Maio
Luigi Laghi
Fabio Grizzi
Tessa Fredriksen
Bénédicte Buttard
Mihaela Angelova
Angela Vasaturo
Pauline Maby
Sarah E Church
Helen K Angell
Lucie Lafontaine
Daniela Bruni
Carine El Sissy
Nacilla Haicheur
Amos Kirilovsky
Anne Berger
Christine Lagorce
Jeffrey P Meyers
Christopher Paustian, Laboratory of Molecular and Tumor Immunology, Earle A. Chiles Research Institute, Robert W Franz Cancer Center, Providence Portland Medical Center, Portland, OR, USA.
Zipei Feng, Laboratory of Molecular and Tumor Immunology, Earle A. Chiles Research Institute, Robert W Franz Cancer Center, Providence Portland Medical Center, Portland, OR, USA.Follow
Carmen Ballesteros-Merino, Laboratory of Molecular and Tumor Immunology, Earle A. Chiles Research Institute, Robert W Franz Cancer Center, Providence Portland Medical Center, Portland, OR, USA.Follow
Jeroen Dijkstra
Carlijn van de Water
Shannon van Lent-van Vliet
Nikki Knijn
Ana-Maria Mușină
Dragos-Viorel Scripcariu
Boryana Popivanova
Mingli Xu
Tomonobu Fujita
Shoichi Hazama
Nobuaki Suzuki
Hiroaki Nagano
Kiyotaka Okuno
Toshihiko Torigoe
Noriyuki Sato
Tomohisa Furuhata
Ichiro Takemasa
Kyogo Itoh
Prabhu S Patel
Hemangini H Vora
Birva Shah
Jayendrakumar B Patel
Kruti N Rajvik
Shashank J Pandya
Shilin N Shukla
Yili Wang
Guanjun Zhang
Yutaka Kawakami
Francesco M Marincola
Paolo A Ascierto
Daniel J Sargent
Bernard A Fox, Laboratory of Molecular and Tumor Immunology, Earle A. Chiles Research Institute, Robert W Franz Cancer Center, Providence Portland Medical Center, Portland, OR, USA; Department of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, OR, USA.Follow
Jérôme Galon

Document Type

Article

Publication Date

5-26-2018

Publication Title

Lancet

Keywords

Adult; Aged; Colonic Neoplasms/classification; Colonic Neoplasms/diagnosis; Colonic Neoplasms/immunology; Female; Humans; Lymphocytes, Tumor-Infiltrating; Male; Middle Aged; Neoplasm Recurrence, Local/etiology; Neoplasm Staging; Prognosis; Proportional Hazards Models; Reproducibility of Results

Abstract

BACKGROUND: The estimation of risk of recurrence for patients with colon carcinoma must be improved. A robust immune score quantification is needed to introduce immune parameters into cancer classification. The aim of the study was to assess the prognostic value of total tumour-infiltrating T-cell counts and cytotoxic tumour-infiltrating T-cells counts with the consensus Immunoscore assay in patients with stage I-III colon cancer.

METHODS: An international consortium of 14 centres in 13 countries, led by the Society for Immunotherapy of Cancer, assessed the Immunoscore assay in patients with TNM stage I-III colon cancer. Patients were randomly assigned to a training set, an internal validation set, or an external validation set. Paraffin sections of the colon tumour and invasive margin from each patient were processed by immunohistochemistry, and the densities of CD3+ and cytotoxic CD8+ T cells in the tumour and in the invasive margin were quantified by digital pathology. An Immunoscore for each patient was derived from the mean of four density percentiles. The primary endpoint was to evaluate the prognostic value of the Immunoscore for time to recurrence, defined as time from surgery to disease recurrence. Stratified multivariable Cox models were used to assess the associations between Immunoscore and outcomes, adjusting for potential confounders. Harrell's C-statistics was used to assess model performance.

FINDINGS: Tissue samples from 3539 patients were processed, and samples from 2681 patients were included in the analyses after quality controls (700 patients in the training set, 636 patients in the internal validation set, and 1345 patients in the external validation set). The Immunoscore assay showed a high level of reproducibility between observers and centres (r=0·97 for colon tumour; r=0·97 for invasive margin; p

INTERPRETATION: The Immunoscore provides a reliable estimate of the risk of recurrence in patients with colon cancer. These results support the implementation of the consensus Immunoscore as a new component of a TNM-Immune classification of cancer.

FUNDING: French National Institute of Health and Medical Research, the LabEx Immuno-oncology, the Transcan ERAnet Immunoscore European project, Association pour la Recherche contre le Cancer, CARPEM, AP-HP, Institut National du Cancer, Italian Association for Cancer Research, national grants and the Society for Immunotherapy of Cancer.

Clinical Institute

Cancer

Clinical Institute

Digestive Health

Department

Gastroenterology

Department

Oncology

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