Immune checkpoint inhibition in colorectal cancer: Microsatellite instability and beyond Journal Article


Authors: Cohen, R.; Rousseau, B.; Vidal, J.; Colle, R.; Diaz, L. A. Jr; André, T.
Article Title: Immune checkpoint inhibition in colorectal cancer: Microsatellite instability and beyond
Abstract: Immune checkpoints inhibitors (ICIs) have been a breakthrough, with unique response and survival patterns compared with chemotherapy for patients with advanced Mismatch Repair-deficient/Microsatellite instable (dMMR/MSI) colorectal cancer, but have shown disappointing results in Mismatch Repair-proficient/Microsatellite stable (pMMR/MSS) colorectal cancer. As up to 50% of patients harboring dMMR/MSI advanced cancers will ultimately progress after PD-1 blockade, biomarkers are needed to predict response/resistance to immunotherapy and to select patients for immunomodulating combination therapies. Patients with pMMR/MSS colorectal cancer present with distinct immune profiles compared to dMMR/MSI tumors, giving evidence of different immune escape mechanisms, which could be overcome through individualized immunotherapeutic strategies. In this review we discuss the latest developments in the field of immunotherapy for dMMR/MSI and pMMR/MSS colorectal cancers, and unresolved questions and considerations concerning the use of ICI therapies in this population. Future immunomodulation strategies based on biomarker selection (tumor mutational burden, Immunoscore®, mutational profile) are discussed. © 2019, Springer Nature Switzerland AG.
Keywords: cancer chemotherapy; overall survival; somatic mutation; frameshift mutation; review; bevacizumab; drug efficacy; monotherapy; capecitabine; adjuvant therapy; disease free survival; temozolomide; colorectal cancer; gene; ipilimumab; ticilimumab; unindexed drug; cancer immunotherapy; low drug dose; progression free survival; multiple cycle treatment; cetuximab; cancer resistance; irinotecan; panitumumab; colon cancer; mismatch repair; microsatellite instability; aflibercept; immunomodulation; oxaliplatin; pemetrexed; fluoropyrimidine; metastatic colorectal cancer; tumor escape; response evaluation criteria in solid tumors; trametinib; nivolumab; regorafenib; bms 936559; immunoscore; human; priority journal; copanlisib; binimetinib; pembrolizumab; prognostic assessment; durvalumab; encorafenib; pole gene; atezolizumab; avelumab; mutational load; toripalimab; relatlimab; napabucasin; pexastimogene devacirepvec; rintatolimod; vicriviroc; pold gene
Journal Title: Targeted Oncology
Volume: 15
Issue: 1
ISSN: 1776-2596
Publisher: Springer  
Date Published: 2020-02-01
Start Page: 11
End Page: 24
Language: English
DOI: 10.1007/s11523-019-00690-0
PUBMED: 31786718
PROVIDER: scopus
DOI/URL:
Notes: Review -- Export Date: 1 April 2020 -- Source: Scopus
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  1. Luis Alberto Diaz
    50 Diaz