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; Seong Jun 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

doi:10.3390/cancers14184346

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. ShuklaYili 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, Seong Jun 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

Biostatistics

Research output: Contribution to journal › Article › peer-review

4 Scopus citations

Abstract

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.

Original language	English (US)
Article number	4346
Journal	Cancers
Volume	14
Issue number	18
DOIs	https://doi.org/10.3390/cancers14184346
State	Published - Sep 2022

Keywords

Asian
Immunoscore
MSI
T cell
classification
colon cancer
immune response
prognostic markers
risk stratification
tumor microenvironment

ASJC Scopus subject areas

Oncology
Cancer Research

MD Anderson CCSG core facilities

Biostatistics Resource Group

Access to Document

10.3390/cancers14184346

Cite this

Mlecnik, B., Torigoe, T., Bindea, G., Popivanova, B., Xu, M., Fujita, T., Hazama, S., Suzuki, N., Nagano, H., Okuno, K., Hirohashi, Y., Furuhata, T., Takemasa, I., Patel, P., Vora, H., Shah, B., Patel, J. B., Rajvik, K. N., Pandya, S. J., ... Galon, J. (2022). Clinical Performance of the Consensus Immunoscore in Colon Cancer in the Asian Population from the Multicenter International SITC Study. Cancers, 14(18), Article 4346. https://doi.org/10.3390/cancers14184346

Mlecnik, B, Torigoe, T, Bindea, G, Popivanova, B, Xu, M, Fujita, T, Hazama, S, Suzuki, N, Nagano, H, Okuno, K, Hirohashi, Y, Furuhata, T, Takemasa, I, Patel, P, Vora, H, Shah, B, Patel, JB, Rajvik, KN, Pandya, SJ, Shukla, SN, Wang, Y, Zhang, G, Yoshino, T, Taniguchi, H, Bifulco, C, Lugli, A, 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, MHA, Ohashi, PS, Nguyen, LT, Han, SJ, MacGregor, HL, Hafezi-Bakhtiari, S, Wouters, BG, Masucci, GV, Andersson, E, 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, Marliot, 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, van Lent-van Vliet, S, Knijn, N, Mușină, AM, Scripcariu, DV, Marincola, FM, Ascierto, PA, Fox, BA, Pagès, F, Kawakami, Y & Galon, J 2022, 'Clinical Performance of the Consensus Immunoscore in Colon Cancer in the Asian Population from the Multicenter International SITC Study', Cancers, vol. 14, no. 18, 4346. https://doi.org/10.3390/cancers14184346

@article{b8b1a2aef56f4ec1a5c09e3d5dcc66cd,

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

abstract = "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{\textquoteright}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.",

keywords = "Asian, Immunoscore, MSI, T cell, classification, colon cancer, immune response, prognostic markers, risk stratification, tumor microenvironment",

author = "Bernhard Mlecnik and Toshihiko Torigoe and Gabriela Bindea and Boryana Popivanova and Mingli Xu and Tomonobu Fujita and Shoichi Hazama and Nobuaki Suzuki and Hiroaki Nagano and Kiyotaka Okuno and Yoshihiko Hirohashi and Tomohisa Furuhata and Ichiro Takemasa and Prabhudas Patel and Hemangini Vora and Birva Shah and Patel, {Jayendrakumar B.} and Rajvik, {Kruti N.} and Pandya, {Shashank J.} and Shukla, {Shilin N.} and Yili Wang and Guanjun Zhang and Takayuki Yoshino and Hiroya Taniguchi and Carlo Bifulco and Alessandro Lugli and Lee, {Jiun Kae Jack} and Inti Zlobec and Rau, {Tilman T.} and Berger, {Martin D.} and Nagtegaal, {Iris D.} and Elisa Vink-B{\"o}rger and Arndt Hartmann and Geppert, {Carol I.} and Julie Kolwelter and Susanne Merkel and Robert Gr{\"u}tzmann and {Van den Eynde}, Marc and Anne Jouret-Mourin and Alex Kartheuser and Daniel L{\'e}onard and Christophe Remue and Julia Wang and Prashant Bavi and Roehrl, {Michael H.A.} and Ohashi, {Pamela S.} and Nguyen, {Linh T.} and Han, {Seong Jun} and MacGregor, {Heather L.} and Sara Hafezi-Bakhtiari and Wouters, {Bradly G.} and Masucci, {Giuseppe V.} and Emilia Andersson and Eva Zavadova and Michal Vocka and Jan Spacek and Lubos Petruzelka and Bohuslav Konopasek and Pavel Dundr and Helena Skalova and Kristyna Nemejcova and Gerardo Botti and Fabiana Tatangelo and Paolo Delrio and Gennaro Ciliberto and Michele Maio and Luigi Laghi and Fabio Grizzi and Florence Marliot and Tessa Fredriksen and B{\'e}n{\'e}dicte Buttard and Lucie Lafontaine and Pauline Maby and Amine Majdi and Assia Hijazi and {El Sissy}, Carine and Amos Kirilovsky and Anne Berger and Christine Lagorce and Christopher Paustian and Carmen Ballesteros-Merino and Jeroen Dijkstra and {Van de Water}, Carlijn and {van Lent-van Vliet}, Shannon and Nikki Knijn and Mușin{\u a}, {Ana Maria} and Scripcariu, {Dragos Viorel} and Marincola, {Francesco M.} and Ascierto, {Paolo A.} and Fox, {Bernard A.} and Franck Pag{\`e}s and Yutaka Kawakami and J{\'e}r{\^o}me Galon",

note = "Publisher Copyright: {\textcopyright} 2022 by the authors.",

year = "2022",

month = sep,

doi = "10.3390/cancers14184346",

language = "English (US)",

volume = "14",

journal = "Cancers",

issn = "2072-6694",

publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",

number = "18",

}

TY - JOUR

T1 - Clinical Performance of the Consensus Immunoscore in Colon Cancer in the Asian Population from the Multicenter International SITC Study

AU - Mlecnik, Bernhard

AU - Torigoe, Toshihiko

AU - Bindea, Gabriela

AU - Popivanova, Boryana

AU - Xu, Mingli

AU - Fujita, Tomonobu

AU - Hazama, Shoichi

AU - Suzuki, Nobuaki

AU - Nagano, Hiroaki

AU - Okuno, Kiyotaka

AU - Hirohashi, Yoshihiko

AU - Furuhata, Tomohisa

AU - Takemasa, Ichiro

AU - Patel, Prabhudas

AU - Vora, Hemangini

AU - Shah, Birva

AU - Patel, Jayendrakumar B.

AU - Rajvik, Kruti N.

AU - Pandya, Shashank J.

AU - Shukla, Shilin N.

AU - Wang, Yili

AU - Zhang, Guanjun

AU - Yoshino, Takayuki

AU - Taniguchi, Hiroya

AU - Bifulco, Carlo

AU - Lugli, Alessandro

AU - Lee, Jiun Kae Jack

AU - Zlobec, Inti

AU - Rau, Tilman T.

AU - Berger, Martin D.

AU - Nagtegaal, Iris D.

AU - Vink-Börger, Elisa

AU - Hartmann, Arndt

AU - Geppert, Carol I.

AU - Kolwelter, Julie

AU - Merkel, Susanne

AU - Grützmann, Robert

AU - Van den Eynde, Marc

AU - Jouret-Mourin, Anne

AU - Kartheuser, Alex

AU - Léonard, Daniel

AU - Remue, Christophe

AU - Wang, Julia

AU - Bavi, Prashant

AU - Roehrl, Michael H.A.

AU - Ohashi, Pamela S.

AU - Nguyen, Linh T.

AU - Han, Seong Jun

AU - MacGregor, Heather L.

AU - Hafezi-Bakhtiari, Sara

AU - Wouters, Bradly G.

AU - Masucci, Giuseppe V.

AU - Andersson, Emilia

AU - Zavadova, Eva

AU - Vocka, Michal

AU - Spacek, Jan

AU - Petruzelka, Lubos

AU - Konopasek, Bohuslav

AU - Dundr, Pavel

AU - Skalova, Helena

AU - Nemejcova, Kristyna

AU - Botti, Gerardo

AU - Tatangelo, Fabiana

AU - Delrio, Paolo

AU - Ciliberto, Gennaro

AU - Maio, Michele

AU - Laghi, Luigi

AU - Grizzi, Fabio

AU - Marliot, Florence

AU - Fredriksen, Tessa

AU - Buttard, Bénédicte

AU - Lafontaine, Lucie

AU - Maby, Pauline

AU - Majdi, Amine

AU - Hijazi, Assia

AU - El Sissy, Carine

AU - Kirilovsky, Amos

AU - Berger, Anne

AU - Lagorce, Christine

AU - Paustian, Christopher

AU - Ballesteros-Merino, Carmen

AU - Dijkstra, Jeroen

AU - Van de Water, Carlijn

AU - van Lent-van Vliet, Shannon

AU - Knijn, Nikki

AU - Mușină, Ana Maria

AU - Scripcariu, Dragos Viorel

AU - Marincola, Francesco M.

AU - Ascierto, Paolo A.

AU - Fox, Bernard A.

AU - Pagès, Franck

AU - Kawakami, Yutaka

AU - Galon, Jérôme

PY - 2022/9

Y1 - 2022/9

N2 - 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.

AB - 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.

KW - Asian

KW - Immunoscore

KW - MSI

KW - T cell

KW - classification

KW - colon cancer

KW - immune response

KW - prognostic markers

KW - risk stratification

KW - tumor microenvironment

UR - http://www.scopus.com/inward/record.url?scp=85138700184&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85138700184&partnerID=8YFLogxK

U2 - 10.3390/cancers14184346

DO - 10.3390/cancers14184346

M3 - Article

C2 - 36139506

AN - SCOPUS:85138700184

SN - 2072-6694

VL - 14

JO - Cancers

JF - Cancers

IS - 18

M1 - 4346

ER -

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

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Keywords

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MD Anderson CCSG core facilities

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