Multicenter International Society for Immunotherapy of Cancer Study of the Consensus Immunoscore for the Prediction of Survival and Response to Chemotherapy in Stage III Colon Cancer

Mlecnik B, Bifulco C, Bindea G, Marliot F, Lugli A, Lee JJ, Zlobec I, Rau TT, Berger MD, Nagtegaal ID, Vink-Borger E, Hartmann A, Geppert CI, Kolwelter J, Merkel S, Grützmann R, Van Den Eynde M, Jouret-Mourin A, Kartheuser A, Leonard D, Remue C, Wang JY, Bavi P, Roehrl MHA, Ohashi PS, Nguyen LT, Han S, Macgregor HL, Hafezi-Bakhtiari S, Wouters BG, Masucci GV, Andersson EK, Zavadova E, Vocka M, Spacek J, Petruzelka L, Konopasek B, Dundr P, Skalova H, Nemejcova K, Botti G, Tatangelo F, Delrio P, Ciliberto G, Maio M, Laghi L, Grizzi F, Fredriksen T, Buttard B, Lafontaine L, Bruni D, Lanzi A, El Sissy C, Haicheur N, Kirilovsky A, Berger A, Lagorce C, Paustian C, Ballesteros-Merino C, Dijkstra J, Van De Water C, Van Lent-Van Vliet S, Knijn N, Musina AM, Scripcariu DV, Popivanova B, Xu M, Fujita T, Hazama S, Suzuki N, Nagano H, Okuno K, Torigoe T, Sato N, Furuhata T, Takemasa I, Itoh K, Patel PS, Vora HH, Shah B, Patel JB, Rajvik KN, Pandya SJ, Shukla SN, Wang Y, Zhang G, Kawakami Y, Marincola FM, Ascierto PA, Fox BA, Pages F, Galon J (2020)

Publication Type: Journal article

Publication year: 2020


Book Volume: 38

Pages Range: 3638-+

Journal Issue: 31

DOI: 10.1200/JCO.19.03205


PURPOSEThe purpose of this study was to evaluate the prognostic value of Immunoscore in patients with stage III colon cancer (CC) and to analyze its association with the effect of chemotherapy on time to recurrence (TTR).METHODSAn international study led by the Society for Immunotherapy of Cancer evaluated the predefined consensus Immunoscore in 763 patients with American Joint Committee on Cancer/Union for International Cancer Control TNM stage III CC from cohort 1 (Canada/United States) and cohort 2 (Europe/Asia). CD3+ and cytotoxic CD8+ T lymphocyte densities were quantified in the tumor and invasive margin by digital pathology. The primary end point was TTR. Secondary end points were overall survival (OS), disease-free survival (DFS), prognosis in microsatellite stable (MSS) status, and predictive value of efficacy of chemotherapy.RESULTSPatients with a high Immunoscore presented with the lowest risk of recurrence, in both cohorts. Recurrence-free rates at 3 years were 56.9% (95% CI, 50.3% to 64.4%), 65.9% (95% CI, 60.8% to 71.4%), and 76.4% (95% CI, 69.3% to 84.3%) in patients with low, intermediate, and high immunoscores, respectively (hazard ratio [HR; high v low], 0.48; 95% CI, 0.32 to 0.71; P = .0003). Patients with high Immunoscore showed significant association with prolonged TTR, OS, and DFS (all P < .001). In Cox multivariable analysis stratified by participating center, Immunoscore association with TTR was independent (HR [high v low], 0.41; 95% CI, 0.25 to 0.67; P = .0003) of patient's sex, T stage, N stage, sidedness, and microsatellite instability status. Significant association of a high Immunoscore with prolonged TTR was also found among MSS patients (HR [high v low], 0.36; 95% CI, 0.21 to 0.62; P = .0003). Immunoscore had the strongest contribution 2 proportion for influencing survival (TTR and OS). Chemotherapy was significantly associated with survival in the high-Immunoscore group for both low-risk (HR [chemotherapy v no chemotherapy], 0.42; 95% CI, 0.25 to 0.71; P = .0011) and high-risk (HR [chemotherapy v no chemotherapy], 0.5; 95% CI, 0.33 to 0.77; P = .0015) patients, in contrast to the low-Immunoscore group (P > .12).CONCLUSIONThis study shows that a high Immunoscore significantly associated with prolonged survival in stage III CC. Our findings suggest that patients with a high Immunoscore will benefit the most from chemotherapy in terms of recurrence risk.

Authors with CRIS profile

Involved external institutions

Univerzita Karlova v Praze / Charles University in Prague CZ Czech Republic (CZ) Université Catholique de Louvain (UCL) BE Belgium (BE) Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale" IT Italy (IT) Cliniques universitaires Saint-Luc (CHU St-Luc) BE Belgium (BE) General University Hospital in Prague / Všeobecná Fakultní Nemocnice v Praze (VFN) CZ Czech Republic (CZ) University of Texas MD Anderson Cancer Center US United States (USA) (US) National Institute for Health and Medical Research / Institut national de la santé et de la recherche médicale (INSERM) FR France (FR) Universität Bern CH Switzerland (CH) Radboud University Nijmegen Medical Centre / Radboudumc of voluit Radboud Universitair Medisch Centrum (UMC) NL Netherlands (NL) Karolinska Institute SE Sweden (SE) University Health Network (UHN) CA Canada (CA) Inselspital, Universitätsspital Bern CH Switzerland (CH) University of Toronto CA Canada (CA) Grigore T. Popa University of Medicine and Pharmacy / Universitatea de Medicină și Farmacie "Grigore T. Popa" (UMF Iași) RO Romania (RO) Sapporo Medical University / 札幌医科大学 JP Japan (JP) University of Parma / Università degli Studi di Parma IT Italy (IT) Gujarat Cancer & Research Institute IN India (IN) Yamaguchi University JP Japan (JP) University Hospital Siena IT Italy (IT) Oregon Health and Science University (OSHU) US United States (USA) (US) Providence Portland Medical Center US United States (USA) (US) Keio University / 慶應義塾大学 JP Japan (JP) Istituto Nazionale Tumori Regina Elena (IRE) IT Italy (IT) Kindai University / 近畿大学 JP Japan (JP) Xi’an Jiaotong-Liverpool University (XJTLU) CN China (CN) Georges Pompidou European Hospital / Hôpital Européen Georges-Pompidou (HEGP) FR France (FR) Kurume University / 久留米大学 JP Japan (JP) Curandis Laboratories LLC US United States (USA) (US) Istituto Clinico Humanitas IT Italy (IT)

How to cite


Mlecnik, B., Bifulco, C., Bindea, G., Marliot, F., Lugli, A., Lee, J.J.,... Galon, J. (2020). Multicenter International Society for Immunotherapy of Cancer Study of the Consensus Immunoscore for the Prediction of Survival and Response to Chemotherapy in Stage III Colon Cancer. Journal of Clinical Oncology, 38(31), 3638-+.


Mlecnik, Bernhard, et al. "Multicenter International Society for Immunotherapy of Cancer Study of the Consensus Immunoscore for the Prediction of Survival and Response to Chemotherapy in Stage III Colon Cancer." Journal of Clinical Oncology 38.31 (2020): 3638-+.

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