Immunopathologic stratification of colorectal cancer for checkpoint blockade immunotherapy Journal Article


Authors: Llosa, N. J.; Luber, B.; Siegel, N.; Awan, A. H.; Oke, T.; Zhu, Q.; Bartlett, B. R.; Aulakh, L. K.; Thompson, E. D.; Jaffee, E. M.; Durham, J. N.; Sears, C. L.; Le, D. T.; Diaz, L. A. Jr; Pardoll, D. M.; Wang, H.; Housseau, F.; Anders, R. A.
Article Title: Immunopathologic stratification of colorectal cancer for checkpoint blockade immunotherapy
Abstract: Mismatch-repair deficiency in solid tumors predicts their response to PD-1 blockade. Based on this principle, pembrolizumab is approved as standard of care for patients with unresectable or metastatic microsatellite instability–high (MSI-H) cancer. Despite this success, a large majority of metastatic colorectal cancer patients are not MSI-H and do not benefit from checkpoint blockade treatment. Predictive biomarkers to develop personalized medicines and guide clinical trials are needed for these patients. We, therefore, asked whether immunohistologic stratification of metastatic colorectal cancer based on primary tumor PD-L1 expression associated with the presence or absence of extracellular mucin defines a subset of metastatic colorectal cancer patients who exhibit a preexisting antitumor immune response and who could potentially benefit from the checkpoint blockade. To address this, we studied 26 advanced metastatic colorectal cancer patients treated with pembrolizumab (NCT01876511). To stratify patients, incorporation of histopathologic characteristics (percentage of extracellular mucin) and PD-L1 expression at the invasive front were used to generate a composite score, the CPM (composite PD-L1 and mucin) score, which discriminated patients who exhibited clinical benefit (complete, partial, or stable disease) from those patients with progressive disease. When validated in larger cohorts, the CPM score in combination with MSI testing may guide immunotherapy interventions for colorectal cancer patient treatment. © 2019 American Association for Cancer Research.
Journal Title: Cancer Immunology Research
Volume: 7
Issue: 10
ISSN: 2326-6066
Publisher: American Association for Cancer Research  
Date Published: 2019-10-01
Start Page: 1574
End Page: 1579
Language: English
DOI: 10.1158/2326-6066.Cir-18-0927
PUBMED: 31439614
PROVIDER: scopus
PMCID: PMC6774859
DOI/URL:
Notes: Article -- Export Date: 1 November 2019 -- Source: Scopus
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  1. Luis Alberto Diaz
    48 Diaz