Multicenter International Study of the Consensus Immunoscore for the Prediction of Relapse and Survival in Early-Stage Colon Cancer

Mlecnik B, Lugli A, Bindea G, Marliot F, Bifulco C, Lee JKJ, Zlobec I, Rau TT, Berger MD, Nagtegaal ID, Vink-Börger E, Hartmann A, Geppert CI, Kolwelter J, Merkel S, Grützmann R, Van den Eynde M, Jouret-Mourin A, Kartheuser A, Léonard D, Remue C, Wang J, Bavi P, Roehrl MH, Ohashi PS, Nguyen LT, Han SJ, 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, Maby P, Majdi A, Hijazi A, El Sissy C, Kirilovsky A, Berger A, Lagorce C, Paustian C, Ballesteros-Merino C, Dijkstra J, van de Water C, Vliet SvLv, Knijn N, Mușină 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, Patel P, Vora HH, Shah B, Patel JB, Rajvik KN, Pandya SJ, Shukla SN, Wang Y, Zhang G, Kawakami Y, Marincola FM, Ascierto PA, Fox BA, Pagès F, Galon J (2023)

Publication Type: Journal article

Publication year: 2023

Journal

Book Volume: 15

Article Number: 418

Journal Issue: 2

DOI: 10.3390/cancers15020418

Abstract

Background: The prognostic value of Immunoscore was evaluated in Stage II/III colon cancer (CC) patients, but it remains unclear in Stage I/II, and in early-stage subgroups at risk. An international Society for Immunotherapy of Cancer (SITC) study evaluated the pre-defined consensus Immunoscore in tumors from 1885 AJCC/UICC-TNM Stage I/II CC patients from Canada/USA (Cohort 1) and Europe/Asia (Cohort 2). METHODS: Digital-pathology is used to quantify the densities of CD3+ and CD8+ T-lymphocyte in the center of tumor (CT) and the invasive margin (IM). The time to recurrence (TTR) was the primary endpoint. Secondary endpoints were disease-free survival (DFS), overall survival (OS), prognosis in Stage I, Stage II, Stage II-high-risk, and microsatellite-stable (MSS) patients. RESULTS: High-Immunoscore presented with the lowest risk of recurrence in both cohorts. In Stage I/II, recurrence-free rates at 5 years were 78.4% (95%-CI, 74.4–82.6), 88.1% (95%-CI, 85.7–90.4), 93.4% (95%-CI, 91.1–95.8) in low, intermediate and high Immunoscore, respectively (HR (Hi vs. Lo) = 0.27 (95%-CI, 0.18–0.41); p < 0.0001). In Cox multivariable analysis, the association of Immunoscore to outcome was independent (TTR: HR (Hi vs. Lo) = 0.29, (95%-CI, 0.17–0.50); p < 0.0001) of the patient’s gender, T-stage, sidedness, and microsatellite instability-status (MSI). A significant association of Immunoscore with survival was found for Stage II, high-risk Stage II, T4N0 and MSS patients. The Immunoscore also showed significant association with TTR in Stage-I (HR (Hi vs. Lo) = 0.07 (95%-CI, 0.01–0.61); P = 0.016). The Immunoscore had the strongest (69.5%) contribution χ² for influencing survival. Patients with a high Immunoscore had prolonged TTR in T4N0 tumors even for patients not receiving chemotherapy, and the Immunoscore remained the only significant parameter in multivariable analysis. CONCLUSION: In early CC, low Immunoscore reliably identifies patients at risk of relapse for whom a more intensive surveillance program or adjuvant treatment should be considered.

Authors with CRIS profile

Involved external institutions

National Institute for Health and Medical Research / Institut national de la santé et de la recherche médicale (INSERM) France (FR) Oregon Health and Science University (OSHU) United States (USA) (US) Radboud University Nijmegen Netherlands (NL) Grigore T. Popa University of Medicine and Pharmacy / Universitatea de Medicină și Farmacie "Grigore T. Popa" (UMF Iași) Romania (RO) Keio University Japan (JP) Yamaguchi University Japan (JP) Universität Bern Switzerland (CH) Providence Portland Medical Center United States (USA) (US) University of Texas MD Anderson Cancer Center United States (USA) (US) Inselspital, Universitätsspital Bern Switzerland (CH) Cliniques universitaires Saint-Luc (CHU St-Luc) Belgium (BE) Curandis Laboratories LLC United States (USA) (US) University of Toronto Canada (CA) Karolinska Institute Sweden (SE) General University Hospital in Prague / Všeobecná Fakultní Nemocnice v Praze (VFN) Czech Republic (CZ) Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale" Italy (IT) Istituto di ricovero e cura a carattere scientifico (IRCCS) Italy (IT) Azienda ospedaliero-universitaria Senese Italy (IT) Humanitas Research Hospital / IRCCS Istituto Clinico Humanitas Italy (IT) Sapporo Medical University / 札幌医科大学 Japan (JP) Gujarat Cancer & Research Institute India (IN) Kindai University / 近畿大学 Japan (JP) Xi'an Jiaotong University (XJTU) / 西安交通大学 China (CN)

How to cite

APA:

Mlecnik, B., Lugli, A., Bindea, G., Marliot, F., Bifulco, C., Lee, J.K.J.,... Galon, J. (2023). Multicenter International Study of the Consensus Immunoscore for the Prediction of Relapse and Survival in Early-Stage Colon Cancer. Cancers, 15(2). https://doi.org/10.3390/cancers15020418

MLA:

Mlecnik, Bernhard, et al. "Multicenter International Study of the Consensus Immunoscore for the Prediction of Relapse and Survival in Early-Stage Colon Cancer." Cancers 15.2 (2023).

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