@article{6bc649fae1244451a87984ea7cc6eccc,
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.",
author = "Llosa, {Nicolas J.} and Brandon Luber and Nicholas Siegel and Awan, {Anas H.} and Teniola Oke and Qingfeng Zhu and Bartlett, {Bjarne R.} and Aulakh, {Laveet K.} and Thompson, {Elizabeth D.} and Jaffee, {Elizabeth M.} and Durham, {Jennifer N.} and Sears, {Cynthia L.} and Le, {Dung T.} and Diaz, {Luis A.} and Pardoll, {Drew M.} and Hao Wang and Franck Housseau and Anders, {Robert A.}",
note = "Funding Information: N.J. Llosa reports receiving a commercial research grant from and is a consultant/advisory member for Bristol-Myers Squibb. E.M. Jaffee reports receiving commercial research grants from Aduro Biotech and Bristol-Myers Squibb and is a consultant/advisory board member for CSTONE, DragonFly, and Genocea. C.L. Sears reports receiving a commercial research grant from Bristol-Myers Squibb. D.T. Le reports receiving commercial research grants from Merck and Bristol-Myers Squibb, has received speakers bureau honoraria from Merck, and is a consultant/advisory board member for Merck and Bristol-Myers Squibb. L.A. Diaz reports receiving a commercial research grant from Merck, has ownership interest (including patents) in PGDx, Amgen, Thrive, Neophor, and Jounce, and is a consultant/advisory board member for PGDx, Merck, Neophore, and Jounce. D.M. Pardoll reports receiving commercial research grants from Bristol-Myers Squibb, Compugen, and AstraZeneca, has ownership interest (including patents) in DNAtrix, Dracen Pharma, Five Prime Therapeutics, Potenza, Tizona, Trieza, Aduro Biotech, Ervaxx, and WindMil, and is a consultant/advisory board member for Aduro Biotech, Amgen, Merck, Rock Springs Capitol, Tizona, Bayer, Camden Partners, Dynavax, Ervaxx, Five Prime Thera, FLX Bio, Immunomic, and Janssen. F. Housseau reports receiving other commercial research support from Bristol-Meyers Squibb. No potential conflicts of interest were disclosed by the other authors. Funding Information: This work was supported by Bloomberg Philanthropies, the Swim Across America Laboratory at Johns Hopkins, NIH Gastrointestinal Specialized Programs of Research Excellence grant (SPORE; P50 CA062924) and NIH grants P30 DK089502, P30 CA006973, R01 CA203891 (F. Housseau), and T32 CA193145, the Commonwealth Foundation, Cancer Research Institute/Fight Colorectal Cancer, a Stand Up To Cancer Immunology Dream Team Translational Research Grant (SU2C-AACR-DT1012), Merck, Bristol-Myers Squibb, and the Colorectal Cancer Dream Team Translational Research Grant (SU2C-AACR-DT22-17). Stand Up To Cancer is a program of the Entertainment Industry Foundation. Research grants are administered by the American Association for Cancer Research, the scientific partner of SU2C. Publisher Copyright: {\textcopyright} 2019 American Association for Cancer Research.",
year = "2019",
doi = "10.1158/2326-6066.CIR-18-0927",
language = "English (US)",
volume = "7",
pages = "1574--1579",
journal = "Cancer immunology research",
issn = "2326-6066",
publisher = "American Association for Cancer Research Inc.",
number = "10",
}