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
Authors: Mlecnik Bernhard , Bifulco Carlo , Bindea Gabriela , Marliot Florence , Lugli Alessandro , Lee J. Jack , Zlobec Inti , Rau Tilman T. , Berger Martin D. , Nagtegaal Iris D. , Vink-Börger Elisa , Hartmann Arndt , Geppert Carol , Kolwelter Julie , Merkel Susanne , Grützmann Robert , Van den Eynde Marc , Jouret-Mourin Anne , Kartheuser Alex , Léonard Daniel , Remue Christophe , Wang Julia Y. , 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 , Bruni Daniela , Lanzi Anastasia , El Sissy Carine , Haicheur Nacilla , Kirilovsky Amos , Berger Anne , Lagorce Christine , Paustian Christopher , Ballesteros-Merino Carmen , Dijkstra Jeroen , van de Water Carlijn , van Lent–van Vliet Shannon , Knijn Nikki , Muşină 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 , Itoh Kyogo , Patel Prabhu S. , 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: September 2020

PURPOSE The 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). METHODS An 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. RESULTS Patients 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 χ2 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). CONCLUSION This 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.