Beyond the concept of cold and hot tumors for the development of novel predictive biomarkers and the rational design of immunotherapy combination

• Published in: International journal of cancer Vol. 147; no. 6; pp. 1509 - 1518
• Main Authors: De Guillebon, Eleonore, Dardenne, Antoine, Saldmann, Antonin, Séguier, Sylvie, Tran, Thi, Paolini, Lea, Lebbe, Celeste, Tartour, Eric
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 15.09.2020; Wiley Subscription Services, Inc
• Subjects: Antineoplastic Combined Chemotherapy Protocols - pharmacology; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; B7-H1 Antigen - analysis; B7-H1 Antigen - antagonists & inhibitors; B7-H1 Antigen - immunology; B7-H1 Antigen - metabolism; Biomarkers; biomarkers of response; Biomarkers, Tumor - analysis; Biomarkers, Tumor - antagonists & inhibitors; Biomarkers, Tumor - immunology; Biomarkers, Tumor - metabolism; Cancer; CD8 antigen; CD8+T cells; CD8-Positive T-Lymphocytes - drug effects; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; Chemotherapy; Clinical trials; Drug development; Drug Resistance, Neoplasm - drug effects; Drug Resistance, Neoplasm - immunology; Enzyme inhibitors; Humans; Hypoxia; Immune checkpoint inhibitors; Immune Checkpoint Inhibitors - pharmacology; Immune Checkpoint Inhibitors - therapeutic use; Immunotherapy; Lymphocytes T; Lymphocytes, Tumor-Infiltrating - immunology; Medical innovations; Medical research; Myeloid cells; Neoplasms - diagnosis; Neoplasms - drug therapy; Neoplasms - immunology; Patients; PD-L1 protein; Programmed Cell Death 1 Receptor - analysis; Programmed Cell Death 1 Receptor - antagonists & inhibitors; Programmed Cell Death 1 Receptor - immunology; Programmed Cell Death 1 Receptor - metabolism; Protein-tyrosine kinase; Radiation therapy; Tumor Microenvironment - drug effects; Tumor Microenvironment - immunology; Tumors; CD8+T cells; myeloid cells; biomarkers of response; immunotherapy
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.32889

Immunotherapy has revolutionized the management of cancers. At the end of 2018, 1,716 clinical trials assessed regimen that combine program death‐1 (PD‐1)/program death ligand‐1 (PD‐L1) blockers with other cancer therapies (tyrosine kinase inhibitor, chemotherapy and radiotherapy). There is a contrast between these clinical dynamics and the difficulty of identifying biomarkers to better select patients that could benefit from immunotherapy. In this context, different tumor classifications have been proposed to try to better stratify patients. They rely on the characteristics of the tumor microenvironment and led first to divide them into hot and cold tumors. In this review, we aim to demonstrate the limitations of this classification focusing on the differential significance of subpopulations of intratumor CD8 + T cells. We also underline novel mechanisms of resistance to anti‐PD‐1/PD‐L1 blockade, focusing on myeloid cells, hypoxia and tumor immunoediting under treatment. Understanding the mechanisms of resistance to immune‐checkpoint inhibitor is indeed a powerful research driver that allows further identification of novel biomarkers, drug development and bring a rational to innovative therapeutic combinations.