Immunotherapy in colorectal cancer: Rationale, challenges and potential Journal Article

Authors: Ganesh, K.; Stadler, Z. K.; Cercek, A.; Mendelsohn, R. B.; Shia, J.; Segal, N. H.; Diaz, L. A. Jr
Article 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
PUBMED: 30886395
Notes: Review -- Source: Wos
Citation Impact
MSK Authors
  1. Neil Howard Segal
    146 Segal
  2. Zsofia Kinga Stadler
    215 Stadler
  3. Jinru Shia
    542 Shia
  4. Karuna   Ganesh
    25 Ganesh
  5. Luis Alberto Diaz
    50 Diaz