Clinical Performance of the Consensus Immunoscore in Colon Cancer in the Asian Population from the Multicenter International SITC Study

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

CANCERS(2022)

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摘要
Simple Summary Research interest in Immuno-oncology and the role of the adaptative immune system in the progression and prognosis of colon cancer (CC) is growing. In this study, we evaluated the prognostic value of the consensus Immunoscore in 423 patients with AJCC/UICC-TNM stages I-III CC from Asian care centers. Immunoscore (IS) is a bench-to-digital pathology assay that quantifies CD3+ and cytotoxic CD8+ T-lymphocyte densities within the tumor and its invasive margin, stratifying patients into three categories: Low IS, Intermediate IS, and High IS. Multivariable Cox models stratified by center were used to assess the associations between Immunoscore and outcomes, adjusting for potential confounders, including gender, T-stage, N-stage, sidedness, and MSI. A comparison of the performance of risk prediction models was performed using the likelihood ratio test p-value. In uni/multivariable analyses, a High Immunoscore was significantly associated with prolonged survival of CC patients within the Asian population. 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.
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关键词
Immunoscore, colon cancer, tumor microenvironment, immune response, classification, prognostic markers, risk stratification, T cell, MSI, Asian
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