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.

Center for Immuno Oncology University Hospital 53100 Siena Italy

Centre de Recherche des Cordeliers Sorbonne Université Université de Paris 75006 Paris France

Colorectal Surgery Department Instituto Nazionale Tumori IRCCS Fondazione G Pascale 80131 Napoli Italy

Curandis New York NY 10583 USA

Department of Biomedical Sciences Humanitas University Pieve Emanuele 20072 Milan Italy

Department of Biostatistics M D Anderson Cancer Center University of Texas Houston TX 77030 USA

Department of Gastroenterological Breast and Endocrine Surgery Yamaguchi University Graduate School of Medicine Yamaguchi 753 8511 Japan

Department of Immunology and Inflammation IRCCS Humanitas Research Hospital Rozzano 20090 Milan Italy

Department of Laboratory Medicine and Pathobiology University of Toronto Toronto ON M5S 1A8 Canada

Department of Medical Oncology University Hospital of Bern 3010 Bern Switzerland

Department of Medicine and Surgery University of Parma 43125 Parma Italy

Department of Molecular Microbiology and Immunology Oregon Health and Science University Portland OR 97239 USA

Department of Oncology 1st Faculty of Medicine General University Hospital Prague Charles University 12808 Prague Czech Republic

Department of Oncology Pathology Karolinska Institutet Karolinska University 17177 Stockholm Sweden

Department of Pathology AP HP Assistance Publique Hopitaux de Paris Georges Pompidou European Hospital 75015 Paris France

Department of Pathology Cliniques Universitaires St Luc 1200 Brussels Belgium

Department of Pathology Istituto Nazionale Tumori IRCCS Fondazione G Pascale 80131 Napoli Italy

Department of Pathology Laboratory Medicine Program University Health Network 11 E444 Toronto ON M5G 2C4 Canada

Department of Pathology Memorial Sloan Kettering Cancer Center New York NY 10065 USA

Department of Pathology Providence Portland Medical Center Portland OR 97213 USA

Department of Pathology Sapporo Medical University Sapporo 060 8556 Japan

Department of Pathology University Erlangen Nürnberg 91054 Erlangen Germany

Department of Surgery School of Medicine Kindai University Osaka sayama 589 0014 Japan

Department of Surgery Surgical Oncology and Science Sapporo Medical University Sapporo 060 8556 Japan

Department of Surgery University Erlangen Nürnberg 91054 Erlangen Germany

Department of Surgical Oncology Regional Institute of Oncology University of Medicine and Pharmacy Grigore T Popa 700115 Iaşi Romania

Department of Translational Research and Developmental Therapeutics against Cancer Yamaguchi University School of Medicine Yamaguchi 755 8505 Japan

Digestive Surgery Department AP HP Assistance Publique Hopitaux de Paris Georges Pompidou European Hospital 75015 Paris France

Division of Cellular Signaling Institute for Advanced Medical Research School of Medicine Keio University Tokyo 160 8582 Japan

Equipe Labellisée Ligue Contre le Cancer 75006 Paris France

Health Science Center of Xi'an Jiaotong University Xi'an 710061 China

Immunomonitoring Platform Laboratory of Immunology AP HP Assistance Publique Hopitaux de Paris Georges Pompidou European Hospital 75015 Paris France

Inovarion 75005 Paris France

INSERM Laboratory of Integrative Cancer Immunology 75006 Paris France

Institut de Recherche Clinique et Experimentale Université Catholique de Louvain 1200 Brussels Belgium

Institut Roi Albert 2 Department of Digestive Surgery Cliniques Universitaires St Luc Université Catholique de Louvain 1200 Brussels Belgium

Institut Roi Albert 2 Department of Medical Oncology Cliniques Universitaires St Luc 1200 Brussels Belgium

Institute for Cancer Research School of Basic Medical Science Xi'an 710061 China

Institute of Pathology 1st Faculty of Medicine General University Hospital Prague Charles University 12808 Prague Czech Republic

Institute of Pathology University of Bern 3008 Bern Switzerland

IRCCS Istituto Nazionale Tumori Regina Elena 00128 Rome Italy

Kite Pharma Santa Monica CA 90404 USA

Laboratory of Molecular and Tumor Immunology Earle A Chiles Research Institute Robert W Franz Cancer Center Providence Portland Medical Center Portland OR 97213 USA

Laboratory of Molecular Gastroenterology IRCCS Humanitas Research Hospital Rozzano 20090 Milan Italy

Melanoma Cancer Immunotherapy and Innovative Therapies Unit Istituto Nazionale Tumori IRCCS Fondazione G Pascale 80131 Napoli Italy

Pathology Department Radboud University 6500 HC Nijmegen The Netherlands

Princess Margaret Cancer Centre Toronto ON M5G 2C1 Canada

The Gujarat Cancer and Research Institute Asarwa Ahmedabad 380016 India

Zobrazit více v PubMed

Galon J., Mlecnik B., Bindea G., Angell H.K., Berger A., Lagorce C., Lugli A., Zlobec I., Hartmann A., Bifulco C., et al. Towards the introduction of the ‘Immunoscore’ in the classification of malignant tumours. J. Pathol. 2014;232:199–209. doi: 10.1002/path.4287. PubMed DOI PMC

Guinney J., Dienstmann R., Wang X., De Reyniès A., Schlicker A., Soneson C., Marisa L., Roepman P., Nyamundanda G., Angelino P., et al. The consensus molecular subtypes of colorectal cancer. Nat. Med. 2015;21:1350–1356. doi: 10.1038/nm.3967. PubMed DOI PMC

Kitajima K., Fujimori T., Fujii S., Takeda J., Ohkura Y., Kawamata H., Kumamoto T., Ishiguro S., Kato Y., Shimoda T., et al. Correlations between lymph node metastasis and depth of submucosal invasion in submucosal invasive colorectal carcinoma: A Japanese collaborative study. J. Gastroenterol. 2004;39:534–543. doi: 10.1007/s00535-004-1339-4. PubMed DOI

Tateishi Y., Nakanishi Y., Taniguchi H., Shimoda T., Umemura S. Pathological prognostic factors predicting lymph node metastasis in submucosal invasive (T1) colorectal carcinoma. Mod. Pathol. 2010;23:1068–1072. doi: 10.1038/modpathol.2010.88. PubMed DOI

Yamamoto S., Watanabe M., Hasegawa H., Baba H., Yoshinare K., Shiraishi J., Kitajima M. The risk of lymph node metastasis in T1 colorectal carcinoma. Hepato Gastroenterol. 2004;51:998–1000. PubMed

Ueno H., Hashiguchi Y., Kajiwara Y., Shinto E., Shimazaki H., Kurihara H., Mochizuki H., Hase K. Proposed Objective Criteria for “Grade 3” in Early Invasive Colorectal Cancer. Am. J. Clin. Pathol. 2010;134:312–322. doi: 10.1309/AJCPMQ7I5ZTTZSOM. PubMed DOI

Lugli A., Kirsch R., Ajioka Y., Bosman F., Cathomas G., Dawson H., El Zimaity H., Fléjou J.-F., Hansen T.P., Hartmann A., et al. Recommendations for reporting tumor budding in colorectal cancer based on the International Tumor Budding Consensus Conference (ITBCC) 2016. Mod. Pathol. 2017;30:1299–1311. doi: 10.1038/modpathol.2017.46. PubMed DOI

Rogers A., Winter D.C., Heeney A., Gibbons D., Lugli A., Puppa G., Sheahan K. Systematic review and meta-analysis of the impact of tumour budding in colorectal cancer. Br. J. Cancer. 2016;115:831–840. doi: 10.1038/bjc.2016.274. PubMed DOI PMC

Zlobec I., Berger M.D., Lugli A. Tumour budding and its clinical implications in gastrointestinal cancers. Br. J. Cancer. 2020;123:700–708. doi: 10.1038/s41416-020-0954-z. PubMed DOI PMC

Marliot F., Chen X., Kirilovsky A., Sbarrato T., El Sissy C., Batista L., Van den Eynde M., Haicheur-Adjouri N., Anitei M.-G., Musina A.-M., et al. Analytical validation of the Immunoscore and its associated prognostic value in patients with colon cancer. J. Immunother. Cancer. 2020;8:e000272. doi: 10.1136/jitc-2019-000272. PubMed DOI PMC

Marliot F., Lafontaine L., Galon J. Immunoscore assay for the immune classification of solid tumors: Technical aspects, improvements and clinical perspectives. Methods Enzym. 2020;636:109–128. doi: 10.1016/bs.mie.2019.07.018. PubMed DOI

Pagès F., Mlecnik B., Marliot F., Bindea G., Ou F.-S., Bifulco C., Lugli A., Zlobec I., Rau T.T., Berger M.D., et al. International validation of the consensus Immunoscore for the classification of colon cancer: A prognostic and accuracy study. Lancet. 2018;391:2128–2139. doi: 10.1016/S0140-6736(18)30789-X. PubMed DOI

Fridman W.H., Pagès F., Sautes-Fridman C., Galon J. The immune contexture in human tumours: Impact on clinical outcome. Nat. Rev. Cancer. 2012;12:298–306. doi: 10.1038/nrc3245. PubMed DOI

Galon J., Angell H.K., Bedognetti D., Marincola F.M. The Continuum of Cancer Immunosurveillance: Prognostic, Predictive, and Mechanistic Signatures. Immunity. 2013;39:11–26. doi: 10.1016/j.immuni.2013.07.008. PubMed DOI

Galon J., Costes A., Sanchez-Cabo F., Kirilovsky A., Mlecnik B., Lagorce-Pagès C., Tosolini M., Camus M., Berger A., Wind P., et al. Type, Density, and Location of Immune Cells Within Human Colorectal Tumors Predict Clinical Outcome. Science. 2006;313:1960–1964. doi: 10.1126/science.1129139. PubMed DOI

Koelzer V.H., Dawson H., Andersson E., Karamitopoulou E., Masucci G.V., Lugli A., Zlobec I. Active immunosurveillance in the tumor microenvironment of colorectal cancer is associated with low frequency tumor budding and improved outcome. Transl. Res. 2015;166:207–217. doi: 10.1016/j.trsl.2015.02.008. PubMed DOI

Laghi L., Bianchi P., Miranda E., Balladore E., Pacetti V., Grizzi F., Allavena P., Torri V., Repici A., Santoro A., et al. CD3+ cells at the invasive margin of deeply invading (pT3–T4) colorectal cancer and risk of post-surgical metastasis: A longitudinal study. Lancet Oncol. 2009;10:877–884. doi: 10.1016/S1470-2045(09)70186-X. PubMed DOI

Lee W.-S., Park S., Lee W.Y., Yun S.H., Chun H.-K. Clinical impact of tumor-infiltrating lymphocytes for survival in stage II colon cancer. Cancer. 2010;116:5188–5199. doi: 10.1002/cncr.25293. PubMed DOI

Mlecnik B., Bindea G., Angell H.K., Maby P., Angelova M., Tougeron D., Church S.E., Lafontaine L., Fischer M., Fredriksen T., et al. Integrative Analyses of Colorectal Cancer Show Immunoscore Is a Stronger Predictor of Patient Survival Than Microsatellite Instability. Immunity. 2016;44:698–711. doi: 10.1016/j.immuni.2016.02.025. PubMed DOI

Mlecnik B., Bindea G., Angell H.K., Sasso M.S., Obenauf A.C., Fredriksen T., Lafontaine L., Bilocq A.M., Kirilovsky A., Tosolini M., et al. Functional Network Pipeline Reveals Genetic Determinants Associated with in Situ Lymphocyte Proliferation and Survival of Cancer Patients. Sci. Transl. Med. 2014;6:228ra37. doi: 10.1126/scitranslmed.3007240. PubMed DOI

Mlecnik B., Tosolini M., Kirilovsky A., Berger A., Bindea G., Meatchi T., Bruneval P., Trajanoski Z., Fridman W.-H., Pagès F., et al. Histopathologic-Based Prognostic Factors of Colorectal Cancers Are Associated with the State of the Local Immune Reaction. J. Clin. Oncol. 2011;29:610–618. doi: 10.1200/JCO.2010.30.5425. PubMed DOI

Nosho K., Baba Y., Tanaka N., Shima K., Hayashi M., Meyerhardt J.A., Giovannucci E., Dranoff G., Fuchs C.S., Ogino S. Tumour-infiltrating T-cell subsets, molecular changes in colorectal cancer and prognosis: Cohort study and literature review. J. Pathol. 2010;222:350–366. doi: 10.1002/path.2774. PubMed DOI PMC

Ogino S., Galon J., Fuchs C.S., Dranoff G. Cancer immunology—Analysis of host and tumor factors for personalized medicine. Nat. Rev. Clin. Oncol. 2011;8:711–719. doi: 10.1038/nrclinonc.2011.122. PubMed DOI PMC

Ogino S., Nosho K., Irahara N., Meyerhardt J.A., Baba Y., Shima K., Glickman J.N., Ferrone C.R., Mino-Kenudson M., Tanaka N., et al. Lymphocytic Reaction to Colorectal Cancer Is Associated with Longer Survival, Independent of Lymph Node Count, Microsatellite Instability, and CpG Island Methylator Phenotype. Clin. Cancer Res. 2009;15:6412–6420. doi: 10.1158/1078-0432.CCR-09-1438. PubMed DOI PMC

Pages F., Berger A., Camus M., Sanchez-Cabo F., Costes A., Molidor R., Mlecnik B., Kirilovsky A., Nilsson M., Damotte D., et al. Effector memory T cells, early metastasis, and survival in colorectal cancer. N. Engl. J. Med. 2005;353:2654–2666. doi: 10.1056/NEJMoa051424. PubMed DOI

Pagès F., Kirilovsky A., Mlecnik B., Asslaber M., Tosolini M., Bindea G., Lagorce C., Wind P., Marliot F., Bruneval P., et al. In Situ Cytotoxic and Memory T Cells Predict Outcome in Patients with Early-Stage Colorectal Cancer. J. Clin. Oncol. 2009;27:5944–5951. doi: 10.1200/JCO.2008.19.6147. PubMed DOI

Sinicrope F.A., Rego R.L., Ansell S.M., Knutson K.L., Foster N.R., Sargent D.J. Intraepithelial effector (CD3+)/regulatory (FoxP3+) T-cell ratio predicts a clinical outcome of human colon carcinoma. Gastroenterology. 2009;137:1270–1279. doi: 10.1053/j.gastro.2009.06.053. PubMed DOI PMC

Galon J., Fridman W.-H., Pagès F. The Adaptive Immunologic Microenvironment in Colorectal Cancer: A Novel Perspective. Cancer Res. 2007;67:1883–1886. doi: 10.1158/0008-5472.CAN-06-4806. PubMed DOI

Bindea G., Mlecnik B., Fridman W.-H., Galon J. The prognostic impact of anti-cancer immune response: A novel classification of cancer patients. Semin. Immunopathol. 2011;33:335–340. doi: 10.1007/s00281-011-0264-x. PubMed DOI PMC

Fridman W.-H., Dieu-Nosjean M.-C., Pagès F., Cremer I., Damotte D., Sautès-Fridman C., Galon J. The Immune Microenvironment of Human Tumors: General Significance and Clinical Impact. Cancer Microenviron. 2013;6:117–122. doi: 10.1007/s12307-012-0124-9. PubMed DOI PMC

Pagès F., Galon J., Fridman W.H. The essential role of the in situ immune reaction in human colorectal cancer. J. Leukoc. Biol. 2008;84:981–987. doi: 10.1189/jlb.1107773. PubMed DOI

Angelova M., Mlecnik B., Vasaturo A., Bindea G., Fredriksen T., Lafontaine L., Buttard B., Morgand E., Bruni D., Jouret-Mourin A., et al. Evolution of Metastases in Space and Time under Immune Selection. Cell. 2018;175:751–765.e16. doi: 10.1016/j.cell.2018.09.018. PubMed DOI

Berghoff A.S., Fuchs E., Ricken G., Mlecnik B., Bindea G., Spanberger T., Hackl M., Widhalm G., Dieckmann K., Prayer D., et al. Density of tumor-infiltrating lymphocytes correlates with extent of brain edema and overall survival time in patients with brain metastases. Oncoimmunology. 2016;5:e1057388. doi: 10.1080/2162402X.2015.1057388. PubMed DOI PMC

Mlecnik B., Bindea G., Kirilovsky A., Angell H.K., Obenauf A.C., Tosolini M., Church S.E., Maby P., Vasaturo A., Angelova M., et al. The tumor microenvironment and Immunoscore are critical determinants of dissemination to distant metastasis. Sci. Transl. Med. 2016;8:327ra26. doi: 10.1126/scitranslmed.aad6352. PubMed DOI

Mlecnik B., Van Den Eynde M., Bindea G., Church S.E., Vasaturo A., Fredriksen T., Lafontaine L., Haicheur N., Marliot F., Debetancourt D., et al. Comprehensive Intrametastatic Immune Quantification and Major Impact of Immunoscore on Survival. J. Natl. Cancer Inst. 2018;110:97–108. doi: 10.1093/jnci/djx123. PubMed DOI

Van den Eynde M., Mlecnik B., Bindea G., Fredriksen T., Church S.E., Lafontaine L., Haicheur N., Marliot F., Angelova M., Vasaturo A., et al. The Link between the Multiverse of Immune Microenvironments in Metastases and the Survival of Colorectal Cancer Patients. Cancer Cell. 2018;34:1012–1026.e3. doi: 10.1016/j.ccell.2018.11.003. PubMed DOI

Bindea G., Mlecnik B., Angell H.K., Galon J. The immune landscape of human tumors: Implications for cancer immunotherapy. Oncoimmunology. 2014;3:e27456. doi: 10.4161/onci.27456. PubMed DOI PMC

Mlecnik B., Bifulco C., Marliot F., Bindea G., Lee J.J., Lugli A., Zlobec I., Rau T.T., Berger M.D., Nagtegaal I.D., et al. Multicenter international SITC study of the consensus Immunoscore for the prediction of survival and response to chemotherapy in Stage III colon cancer. J. Clin. Oncol. 2020. accepted . PubMed PMC

Pagès F., André T., Taieb J., Vernerey D., Henriques J., Borg C., Marliot F., Ben Jannet R., Louvet C., Mineur L., et al. Prognostic and predictive value of the Immunoscore in stage III colon cancer patients treated with oxaliplatin in the prospective IDEA France PRODIGE-GERCOR cohort study. Ann. Oncol. 2020;31:921–929. doi: 10.1016/j.annonc.2020.03.310. PubMed DOI

Sinicrope F.A., Shi Q., Hermitte F., Zemla T.J., Mlecnik B., Benson A.B., Gill S., Goldberg R.M., Kahlenberg M.S., Nair S.G., et al. Contribution of Immunoscore and Molecular Features to Survival Prediction in Stage III Colon Cancer. JNCI Cancer Spectr. 2020;4:pkaa023. doi: 10.1093/jncics/pkaa023. PubMed DOI PMC

Vacchelli E., Senovilla L., Eggermont A., Fridman W.H., Galon J., Zitvogel L., Kroemer G., Galluzzi L. Trial watch: Chemotherapy with immunogenic cell death inducers. Oncoimmunology. 2013;2:e23510. doi: 10.4161/onci.23510. PubMed DOI PMC

Pagès F., Mlecnik B., Galon J. Quantifying Immunoscore performance—Authors’ reply. Lancet. 2018;392:1624–1625. doi: 10.1016/S0140-6736(18)32385-7. PubMed DOI

Uno H., Claggett B., Tian L., Inoue E., Gallo P., Miyata T., Schrag D., Takeuchi M., Uyama Y., Zhao L., et al. Moving Beyond the Hazard Ratio in Quantifying the Between-Group Difference in Survival Analysis. J. Clin. Oncol. 2014;32:2380–2385. doi: 10.1200/JCO.2014.55.2208. PubMed DOI PMC

Galon J., Bruni D. Approaches to treat immune hot, altered and cold tumours with combination immunotherapies. Nat. Rev. Drug Discov. 2019;18:197–218. doi: 10.1038/s41573-018-0007-y. PubMed DOI

Halama N., Michel S., Kloor M., Zoernig I., Benner A., Spille A., Pommerencke T., von Knebel D.M., Folprecht G., Luber B., et al. Localization and Density of Immune Cells in the Invasive Margin of Human Colorectal Cancer Liver Metastases Are Prognostic for Response to Chemotherapy. Cancer Res. 2011;71:5670–5677. doi: 10.1158/0008-5472.CAN-11-0268. PubMed DOI

Vacchelli E., Galluzzi L., Fridman W.H., Galon J., Sautès-Fridman C., Tartour E., Kroemer G. Trial watch: Chemotherapy with immunogenic cell death inducers. Oncoimmunology. 2012;1:179–188. doi: 10.4161/onci.1.2.19026. PubMed DOI PMC

Bindea G., Mlecnik B., Tosolini M., Kirilovsky A., Waldner M., Obenauf A.C., Angell H., Fredriksen T., Lafontaine L., Berger A., et al. Spatiotemporal Dynamics of Intratumoral Immune Cells Reveal the Immune Landscape in Human Cancer. Immunity. 2013;39:782–795. doi: 10.1016/j.immuni.2013.10.003. PubMed DOI

Galon J., Sudarshan C., Ito S., Finbloom D., O’Shea J.J. IL-12 induces IFN regulating factor-1 (IRF-1) gene expression in human NK and T cells. J. Immunol. 1999;162:7256–7262. doi: 10.4049/jimmunol.162.12.7256. PubMed DOI

Mascaux C., Angelova M., Vasaturo A., Beane J., Hijazi K., Anthoine G., Buttard B., Rothe F., Willard-Gallo K., Haller A., et al. Immune evasion before tumour invasion in early lung squamous carcinogenesis. Nature. 2019;571:570–575. doi: 10.1038/s41586-019-1330-0. PubMed DOI

Aranda F., Vacchelli E., Eggermont A., Galon J., Sautes-Fridman C., Tartour E., Zitvogel L., Kroemer G., Galluzzi L. Trial Watch: Peptide vaccines in cancer therapy. Oncoimmunology. 2013;2:e26621. doi: 10.4161/onci.26621. PubMed DOI PMC

Buqué A., Bloy N., Aranda F., Castoldi F., Eggermont A., Cremer I., Fridman W.H., Fucikova J., Galon J., Marabelle A., et al. Trial Watch: Immunomodulatory monoclonal antibodies for oncological indications. Oncoimmunology. 2015;4:e1008814. doi: 10.1080/2162402X.2015.1008814. PubMed DOI PMC

Pol J., Bloy N., Buqué A., Eggermont A., Cremer I., Sautes-Fridman C., Galon J., Tartour E., Zitvogel L., Kroemer G., et al. Trial Watch: Peptide-based anticancer vaccines. Oncoimmunology. 2015;4:e974411. doi: 10.4161/2162402X.2014.974411. PubMed DOI PMC

Vacchelli E., Eggermont A., Fridman W.H., Galon J., Tartour E., Zitvogel L., Kroemer G., Galluzzi L. Trial Watch: Adoptive cell transfer for anticancer immunotherapy. Oncoimmunology. 2013;2:e24238. doi: 10.4161/onci.24238. PubMed DOI PMC

Vacchelli E., Eggermont A., Fridman W.H., Galon J., Zitvogel L., Kroemer G., Galluzzi L. Trial Watch: Immunostimulatory cytokines. Oncoimmunology. 2013;2:e24850. doi: 10.4161/onci.24850. PubMed DOI PMC

Vacchelli E., Eggermont A., Galon J., Sautès-Fridman C., Zitvogel L., Kroemer G., Galluzzi L. Trial watch: Monoclonal antibodies in cancer therapy. Oncoimmunology. 2013;2:e22789. doi: 10.4161/onci.22789. PubMed DOI PMC

Vacchelli E., Galluzzi L., Eggermont A., Galon J., Tartour E., Zitvogel L., Kroemer G. Trial Watch: Immunostimulatory cytokines. Oncoimmunology. 2012;1:493–506. doi: 10.4161/onci.20459. PubMed DOI PMC

Vacchelli E., Martins I., Eggermont A., Fridman W.H., Galon J., Sautès-Fridman C., Tartour E., Zitvogel L., Kroemer G., Galluzzi L. Trial watch: Peptide vaccines in cancer therapy. Oncoimmunology. 2012;1:1557–1576. doi: 10.4161/onci.22428. PubMed DOI PMC

Galon J., Fox B.A., Bifulco C.B., Masucci G., Rau T., Botti G., Marincola F.M., Ciliberto G., Pages F., Ascierto P.A., et al. Immunoscore and Immunoprofiling in cancer: An update from the melanoma and immunotherapy bridge 2015. J. Transl. Med. 2016;14:273. doi: 10.1186/s12967-016-1029-z. PubMed DOI PMC

Gnjatic S., Bronte V., Brunet L.R., Butler M.O., Disis M.L., Galon J., Hakansson L.G., Hanks B.A., Karanikas V., Khleif S.N., et al. Identifying baseline immune-related biomarkers to predict clinical outcome of immunotherapy. J. Immunother. Cancer. 2017;5:44. doi: 10.1186/s40425-017-0243-4. PubMed DOI PMC

Kirilovsky A., Marliot F., El Sissy C., Haicheur N., Galon J., Pagès F. Rational bases for the use of the Immunoscore in routine clinical settings as a prognostic and predictive biomarker in cancer patients. Int. Immunol. 2016;28:373–382. doi: 10.1093/intimm/dxw021. PubMed DOI PMC

Taube J.M., Galon J., Sholl L.M., Rodig S.J., Cottrell T.R., Giraldo N.A., Baras A.S., Patel S.S., Anders R.A., Rimm D.L., et al. Implications of the tumor immune microenvironment for staging and therapeutics. Mod. Pathol. 2018;31:214–234. doi: 10.1038/modpathol.2017.156. PubMed DOI PMC

Galon J., Lanzi A. Immunoscore and its introduction in clinical practice. Q. J. Nucl. Med. Mol. Imaging. 2020;64:152–161. doi: 10.23736/S1824-4785.20.03249-5. PubMed DOI

Angell H.K., Bruni D., Barrett J.C., Herbst R., Galon J. The Immunoscore: Colon Cancer and Beyond. Clin. Cancer Res. 2020;26:332–339. doi: 10.1158/1078-0432.CCR-18-1851. PubMed DOI

Galon J., Bruni D. Tumor Immunology and Tumor Evolution: Intertwined Histories. Immunity. 2020;52:55–81. doi: 10.1016/j.immuni.2019.12.018. PubMed DOI

Argilés G., Tabernero J., Labianca R., Hochhauser D., Salazar R., Iveson T., Laurent-Puig P., Quirke P., Yoshino T., Taieb J., et al. Localised colon cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann. Oncol. 2020;31:1291–1305. doi: 10.1016/j.annonc.2020.06.022. PubMed DOI

Yoshino T., Argilés G., Oki E., Martinelli E., Taniguchi H., Arnold D., Mishima S., Li Y., Smruti B., Ahn J., et al. Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis treatment and follow-up of patients with localised colon cancer. Ann. Oncol. 2021;32:1496–1510. doi: 10.1016/j.annonc.2021.08.1752. PubMed DOI

Multi-Institutional Evaluation of Pathologists' Assessment Compared to Immunoscore