No time to die: the consensus immunoscore for predicting survival and response to chemotherapy of locally advanced colon cancer patients in a multicenter international study

Paolo A Ascierto; Francesco M Marincola; Bernard A Fox; Jérôme Galon

doi:10.1080/2162402X.2020.1826132

No time to die: the consensus immunoscore for predicting survival and response to chemotherapy of locally advanced colon cancer patients in a multicenter international study

Oncoimmunology. 2020 Oct 13;9(1):1826132. doi: 10.1080/2162402X.2020.1826132.

Authors

Paolo A Ascierto¹, Francesco M Marincola², Bernard A Fox^{3

4}, Jérôme Galon^{5

6

7}

Affiliations

¹ Melanoma, Cancer Immunotherapy and Innovative Therapies Unit, Istituto Nazionale Tumori IRCCS Fondazione "G. Pascale", Napoli, Italy.
² Refuge Biotechnologies, Menlo Park, CA, USA.
³ Department of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, OR, USA.
⁴ Laboratory of Molecular and Tumor Immunology, Earle A. Chiles Research Institute, Robert W. Franz Cancer Center, Providence Portland Medical Center, Portland, OR, USA.
⁵ Laboratory of Integrative Cancer Immunology, INSERM, Paris, France.
⁶ Equipe Labellisée Ligue Contre le Cancer, Paris, France.
⁷ Centre de Recherche des Cordeliers, Sorbonne Université, Université de Paris, Paris, France.

Abstract

The multicenter international Society for Immunotherapy of Cancer (SITC) study of the consensus Immunoscore demonstrated the prediction of survival and response to chemotherapy in 763 Stage III colon cancer (CC) patients. Similar Immunoscore groups were found in elderly patients, and densities of immune cells and intratumoral T-cell repertoire were not decreasing with age in the tumor microenvironment. In two independent cohorts, Immunoscore significantly predicted time to recurrence (TTR), disease-free survival (DFS), and overall survival (OS), including within high-risk (T4 or N2) and low-risk (T1-3, N1) patients. In stratified Cox multivariable analysis for TTR, DFS, and OS, Immunoscore's association to outcomes was independent of the patient's age, sidedness, gender, T-stage, N-stage, and microsatellite instability status. Furthermore, the relative contribution to the risk test showed that Immunoscore had the highest contribution to survival. Importantly Immunoscore predicted the likelihood of response to chemotherapy. Only patients with a high-Immunoscore significantly benefited from chemotherapy. The prognostic value of Immunoscore was confirmed in two independent phase 3 clinical trials (NCCTG-N0147, n = 559; Prodige-IDEA, n = 1062). Moreover, results from IDEA phase 3 randomized trial revealed the predictive value of Immunoscore for response to adjuvant FOLFOX chemotherapy duration. The latest edition of the WHO Digestive System Tumors classification introduced the immune response as measured by Immunoscore as essential and desirable diagnostic criteria for CC, and Immunoscore was introduced into the 2020 ESMO Clinical Practice Guidelines for CC to refine the prognosis and adjust chemotherapy decision-making process in stages II and III patients. These results highlight the clinical utility of Immunoscore.

Keywords: Immunoscore; cancer classification; colon cancer; immunity; phase 3 trial; predictive; prognosis; tumor microenvironment.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Aged
Chemotherapy, Adjuvant
Colonic Neoplasms* / drug therapy
Consensus
Humans
Multicenter Studies as Topic
Neoplasm Recurrence, Local*
Neoplasm Staging
Tumor Microenvironment

Grants and funding

The work was supported by INSERM, the LabEx Immuno-oncology, the Transcan ERAnet European project, the Society for Immunotherapy of Cancer (SITC), Association pour la Recherche contre le Cancer (ARC), CARPEM, AP-HP, HalioDx, and Institut National du Cancer, France (INCa).