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Nat Rev Gastroenterol Hepatol. 2019 Jun;16(6):361-375. doi: 10.1038/s41575-019-0126-x.

Immunotherapy in colorectal cancer: rationale, challenges and potential.

Author information

1
Department of Medicine, Memorial Sloan Kettering Cancer Center, York Avenue, New York, NY, USA. ganeshk@mskcc.org.
2
Department of Medicine, Memorial Sloan Kettering Cancer Center, York Avenue, New York, NY, USA.
3
Department of Pathology, Memorial Sloan Kettering Cancer Center, York Avenue, New York, NY, USA.

Abstract

Following initial successes in melanoma treatment, immunotherapy has rapidly become established as a major treatment modality for multiple types of solid cancers, including a subset of colorectal cancers (CRCs). Two programmed cell death 1 (PD1)-blocking antibodies, pembrolizumab and nivolumab, have shown efficacy in patients with metastatic CRC that is mismatch-repair-deficient and microsatellite instability-high (dMMR-MSI-H), and have been granted accelerated FDA approval. In contrast to most other treatments for metastatic cancer, immunotherapy achieves long-term durable remission in a subset of patients, highlighting the tremendous promise of immunotherapy in treating dMMR-MSI-H metastatic CRC. Here, we review the clinical development of immune checkpoint inhibition in CRC leading to regulatory approvals for the treatment of dMMR-MSI-H CRC. We focus on new advances in expanding the efficacy of immunotherapy to early-stage CRC and CRC that is mismatch-repair-proficient and has low microsatellite instability (pMMR-MSI-L) and discuss emerging approaches for targeting the immune microenvironment, which might complement immune checkpoint inhibition.

PMID:
30886395
DOI:
10.1038/s41575-019-0126-x
[Indexed for MEDLINE]

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