BACKGROUND: In this study, we evaluated the prognostic value of Immunoscore in patients with stage I−III colon cancer (CC) in the Asian population. These patients were originally included in an international study led by the Society for Immunotherapy of Cancer (SITC) on 2681 patients with AJCC/UICC-TNM stages I−III CC. METHODS: CD3+ and cytotoxic CD8+ T-lymphocyte densities were quantified in the tumor and invasive margin by digital pathology. The association of Immunoscore with prognosis was evaluated for time to recurrence (TTR), disease-free survival (DFS), and overall survival (OS). RESULTS: Immunoscore stratified Asian patients (n = 423) into different risk categories and was not impacted by age. Recurrence-free rates at 3 years were 78.5%, 85.2%, and 98.3% for a Low, Intermediate, and High Immunoscore, respectively (HR[Low-vs-High] = 7.26 (95% CI 1.75−30.19); p = 0.0064). A High Immunoscore showed a significant association with prolonged TTR, OS, and DFS (p < 0.05). In Cox multivariable analysis stratified by center, Immunoscore association with TTR was independent (HR[Low-vs-Int+High] = 2.22 (95% CI 1.10−4.55) p = 0.0269) of the patient’s gender, T-stage, N-stage, sidedness, and MSI status. A significant association of a High Immunoscore with prolonged TTR was also found among MSS (HR[Low-vs-Int+High] = 4.58 (95% CI 2.27−9.23); p ≤ 0.0001), stage II (HR[Low-vs-Int+High] = 2.72 (95% CI 1.35−5.51); p = 0.0052), low-risk stage-II (HR[Low-vs-Int+High] = 2.62 (95% CI 1.21−5.68); p = 0.0146), and high-risk stage II patients (HR[Low-vs-Int+High] = 3.11 (95% CI 1.39−6.91); p = 0.0055). CONCLUSION: A High Immunoscore is significantly associated with the prolonged survival of CC patients within the Asian population.

Center for Immuno Oncology University Hospital 53100 Siena Italy

Centre de Recherche des Cordeliers Sorbonne Université Université de Paris 75006 Paris France

Colorectal Surgery Department Instituto Nazionale Tumori IRCCS Fondazione G Pascale 80131 Naples Italy

Curandis New York NY 10583 USA

Department of Biomedical Sciences Humanitas University Pieve Emanuele 20072 Milan Italy

Department of Biostatistics M D Anderson Cancer Center University of Texas Houston TX 77030 USA

Department of Gastroenterological Breast and Endocrine Surgery Yamaguchi University Graduate School of Medicine Yamaguchi 753 8511 Japan

Department of Gastroenterology and Gastrointestinal Oncology National Cancer Center Hospital East Kashiwanoha Kashiwa shi 277 8577 Japan

Department of Immunology and Inflammation IRCCS Humanitas Research Hospital Rozzano 20090 Milan Italy

Department of Laboratory Medicine and Pathobiology University of Toronto Toronto ON M5S 1A8 Canada

Department of Medical Oncology University Hospital of Bern 3010 Bern Switzerland

Department of Medicine and Surgery University of Parma 43125 Parma Italy

Department of Molecular Microbiology and Immunology Oregon Health and Science University Portland OR 97239 USA

Department of Oncology 1st Faculty of Medicine General University Hospital Prague Charles University 12808 Prague Czech Republic

Department of Oncology Pathology Karolinska Institutet Karolinska University 17177 Stockholm Sweden

Department of Pathology AP HP Assistance Publique Hopitaux de Paris Georges Pompidou European Hospital 75015 Paris France

Department of Pathology Cliniques Universitaires St Luc 1200 Brussels Belgium

Department of Pathology Istituto Nazionale Tumori IRCCS Fondazione G Pascale 80131 Naples Italy

Department of Pathology Laboratory Medicine Program University Health Network 11 E444 Toronto ON M5G 2C4 Canada

Department of Pathology Memorial Sloan Kettering Cancer Center New York NY 10065 USA

Department of Pathology Providence Portland Medical Center Portland OR 97213 USA

Department of Pathology Sapporo Medical University Sapporo 060 8556 Japan

Department of Pathology University Erlangen Nürnberg 91054 Erlangen Germany

Department of Surgery Kindai University School of Medicine Osakasayama 589 0014 Japan

Department of Surgery Surgical Oncology and Science Sapporo Medical University Sapporo 060 8556 Japan

Department of Surgery University Erlangen Nürnberg 91054 Erlangen Germany

Department of Surgical Oncology Regional Institute of Oncology University of Medicine and Pharmacy Grigore T Popa 700115 Iaşi Romania

Department of Translational Research and Developmental Therapeutics against Cancer Yamaguchi University School of Medicine Yamaguchi 755 8505 Japan

Digestive Surgery Department AP HP Assistance Publique Hopitaux de Paris Georges Pompidou European Hospital 75015 Paris France

Division of Cellular Signaling Institute for Advanced Medical Research School of Medicine Keio University Tokyo 160 8582 Japan

Equipe Labellisée Ligue Contre le Cancer 75006 Paris France

Health Science Center of Xi'an Jiaotong University Xi'an 710061 China

Immunomonitoring Platform Laboratory of Immunology AP HP Assistance Publique Hopitaux de Paris Georges Pompidou European Hospital 75015 Paris France

Inovarion 75005 Paris France

INSERM Laboratory of Integrative Cancer Immunology 75006 Paris France

Institut de Recherche Clinique et Experimentale Université Catholique de Louvain 1200 Brussels Belgium

Institut Roi Albert 2 Department of Digestive Surgery Cliniques Universitaires St Luc Université Catholique de Louvain 1200 Brussels Belgium

Institut Roi Albert 2 Department of Medical Oncology Cliniques Universitaires St Luc 1200 Brussels Belgium

Institute for Cancer Research School of Basic Medical Science Xi'an 710061 China

Institute of Pathology 1st Faculty of Medicine General University Hospital Prague Charles University 12808 Prague Czech Republic

Institute of Pathology University of Bern 3008 Bern Switzerland

IRCCS Istituto Nazionale Tumori Regina Elena 00128 Rome Italy

Kite Pharma Santa Monica CA 90404 USA

Laboratory of Molecular and Tumor Immunology Earle A Chiles Research Institute Robert W Franz Cancer Center Providence Portland Medical Center Portland OR 97213 USA

Laboratory of Molecular Gastroenterology IRCCS Humanitas Research Hospital Rozzano 20090 Milan Italy

Melanoma Cancer Immunotherapy and Innovative Therapies Unit Istituto Nazionale Tumori IRCCS Fondazione G Pascale 80131 Naples Italy

Pathology Department Radboud University 6500 HC Nijmegen The Netherlands

Princess Margaret Cancer Centre Toronto ON M5G 2C1 Canada

The Gujarat Cancer and Research Institute Asarwa Ahmedabad 380016 India

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Multi-Institutional Evaluation of Pathologists' Assessment Compared to Immunoscore