Immunogenomics of Colorectal Cancer Response to Checkpoint Blockade: Analysis of the KEYNOTE 177 Trial and Validation Cohorts

• Published in: Gastroenterology (New York, N.Y. 1943) Vol. 161; no. 4; pp. 1179 - 1193
• Main Authors: Bortolomeazzi, Michele, Keddar, Mohamed Reda, Montorsi, Lucia, Acha-Sagredo, Amelia, Benedetti, Lorena, Temelkovski, Damjan, Choi, Subin, Petrov, Nedyalko, Todd, Katrina, Wai, Patty, Kohl, Johannes, Denner, Tamara, Nye, Emma, Goldstone, Robert, Ward, Sophia, Wilson, Gareth A., Al Bakir, Maise, Swanton, Charles, John, Susan, Miles, James, Larijani, Banafshe, Kunene, Victoria, Fontana, Elisa, Arkenau, Hendrik-Tobias, Parker, Peter J., Rodriguez-Justo, Manuel, Shiu, Kai-Keen, Spencer, Jo, Ciccarelli, Francesca D.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.10.2021; W.B. Saunders
• Subjects: Anti-PD1 Immunotherapy; Antibodies, Monoclonal, Humanized - adverse effects; Antibodies, Monoclonal, Humanized - therapeutic use; Biomarkers, Tumor - genetics; CD8 T cells; CD8-Positive T-Lymphocytes - drug effects; CD8-Positive T-Lymphocytes - immunology; Clinical Trials as Topic; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - genetics; Colorectal Neoplasms - immunology; Cytotoxicity, Immunologic - drug effects; Exome Sequencing; Gene Expression Profiling; Humans; Immune Checkpoint Inhibitors - adverse effects; Immune Checkpoint Inhibitors - therapeutic use; Immunogenetic Phenomena; Immunogenetics; Interferon Gamma; Lymphocytes, Tumor-Infiltrating - drug effects; Lymphocytes, Tumor-Infiltrating - immunology; Mutation; Nivolumab - adverse effects; Nivolumab - therapeutic use; Original Research; Predictive Value of Tests; Programmed Cell Death 1 Receptor - antagonists & inhibitors; Reproducibility of Results; RNA-Seq; Time Factors; Transcriptome; Treatment Outcome; Tumor Microenvironment; Tumor Mutational Burden; Tumor-Associated Macrophages - drug effects; Tumor-Associated Macrophages - immunology; Wnt Signaling; Wnt Signaling; A-FRET; CD; DB-CRC; T-cell; WES; TMB; mIF; TME; GzB; TCGA; Anti-PD1 Immunotherapy; RNA-seq; CRC; SNV; Tumor Mutational Burden; PD1; PDL1; Interferon Gamma; B2M; nDB-CRC; IMC; CD8 T cells

Colorectal cancer (CRC) shows variable response to immune checkpoint blockade, which can only partially be explained by high tumor mutational burden (TMB). We conducted an integrated study of the cancer tissue and associated tumor microenvironment (TME) from patients treated with pembrolizumab (KEYN...