Multicenter International Study of the Consensus Immunoscore for the Prediction of Relapse and Survival in Early-Stage Colon Cancer
Authors: Mlecnik Bernhard , Lugli Alessandro , Bindea Gabriela , Marliot Florence , Bifulco Carlo , Lee Jiun-Kae Jack , Zlobec Inti , Rau Tilman T. , Berger Martin D. , Nagtegaal Iris D. , Vink-Börger Elisa , Hartmann Arndt , Geppert Carol I. , Kolwelter Julie , Merkel Susanne , Grützmann Robert , Van den Eynde Marc , Jouret-Mourin Anne , Kartheuser Alex , Léonard Daniel , Remue Christophe , Wang Julia , Bavi Prashant , Roehrl Michael H. A. , Ohashi Pamela S. , Nguyen Linh T. , Han SeongJun , MacGregor Heather L. , Hafezi-Bakhtiari Sara , Wouters Bradly G. , Masucci Giuseppe V. , Andersson Emilia K. , Zavadova Eva , Vocka Michal , Spacek Jan , Petruzelka Lubos , Konopasek Bohuslav , Dundr Pavel , Skalova Helena , Nemejcova Kristyna , Botti Gerardo , Tatangelo Fabiana , Delrio Paolo , Ciliberto Gennaro , Maio Michele , Laghi Luigi , Grizzi Fabio , Fredriksen Tessa , Buttard Bénédicte , Lafontaine Lucie , Maby Pauline , Majdi Amine , Hijazi Assia , El Sissy Carine , Kirilovsky Amos , Berger Anne , Lagorce Christine , Paustian Christopher , Ballesteros-Merino Carmen , Dijkstra Jeroen , van de Water Carlijn , Vliet Shannon van Lent-van , Knijn Nikki , Mușină Ana-Maria , Scripcariu Dragos-Viorel , Popivanova Boryana , Xu Mingli , Fujita Tomonobu , Hazama Shoichi , Suzuki Nobuaki , Nagano Hiroaki , Okuno Kiyotaka , Torigoe Toshihiko , Sato Noriyuki , Furuhata Tomohisa , Takemasa Ichiro , Patel Prabhu , Vora Hemangini H. , Shah Birva , Patel Jayendrakumar B. , Rajvik Kruti N. , Pandya Shashank J. , Shukla Shilin N. , Wang Yili , Zhang Guanjun , Kawakami Yutaka , Marincola Francesco M. , Ascierto Paolo A. , Fox Bernard A. , Pagès Franck , Galon Jérôme 
Published: January 2023

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.