Immunotherapy in colorectal cancer: Rationale, challenges and potential Review
| Authors: | Ganesh, K.; Stadler, Z. K.; Cercek, A.; Mendelsohn, R. B.; Shia, J.; Segal, N. H.; Diaz, L. A. Jr |
| Review Title: | Immunotherapy in colorectal cancer: Rationale, challenges and potential |
| 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. |
| Keywords: | colon-cancer; phase-i; benefit; tumor-associated macrophages; immune cells; pd-1 blockade; microsatellite instability detection; nivolumab plus ipilimumab; mismatch repair-deficient; durable clinical; promotes t-cell |
| Journal Title: | Nature Reviews Gastroenterology & Hepatology |
| Volume: | 16 |
| Issue: | 6 |
| ISSN: | 1759-5045 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2019-06-01 |
| Start Page: | 361 |
| End Page: | 375 |
| Language: | English |
| ACCESSION: | WOS:000469378000009 |
| DOI: | 10.1038/s41575-019-0126-x |
| PROVIDER: | wos |
| PUBMED: | 30886395 |
| PMCID: | PMC7295073 |
| Notes: | Review -- Source: Wos |
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210Segal -
391Stadler -
352Cercek Hanjis -
720Shia -
75Mendelsohn -
68Ganesh -
149Diaz
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