Aspirin Use and Colorectal Cancer Survival According to Tumor CD274 (Programmed Cell Death 1 Ligand 1) Expression Status.

J Clin Oncol
Authors
Keywords
Abstract

Purpose Blockade of the programmed cell death 1 (PDCD1, PD-1) immune checkpoint pathway can improve clinical outcomes in various malignancies. Evidence suggests that aspirin (a widely used nonsteroidal anti-inflammatory drug) not only prolongs colorectal cancer survival, but can also activate T cell-mediated antitumor immunity and synergize with immunotherapy through inhibition of prostaglandin E2 production. We hypothesized that the survival benefit associated with aspirin might be stronger in colorectal carcinoma with a lower CD274 (PDCD1 ligand 1, PD-L1) expression level that resulted in lower signaling of the immune checkpoint pathway. Patients and Methods Using data from 617 patients with rectal and colon cancer in the Nurses' Health Study and the Health Professionals Follow-Up Study, we examined the association of postdiagnosis aspirin use with patient survival in strata of tumor CD274 expression status measured by immunohistochemistry. We used multivariable Cox proportional hazards regression models to control for potential confounders, including disease stage, microsatellite instability status, CpG island methylator phenotype, long interspersed nucleotide element-1 methylation, cyclooxygenase-2 (PTGS2), and CDX2 expression, and KRAS, BRAF, and PIK3CA mutations. Results The association of postdiagnosis aspirin use with colorectal cancer-specific survival differed by CD274 expression status ( Pinteraction

Year of Publication
2017
Journal
J Clin Oncol
Volume
35
Issue
16
Pages
1836-1844
Date Published
2017 Jun 01
ISSN
1527-7755
DOI
10.1200/JCO.2016.70.7547
PubMed ID
28406723
PubMed Central ID
PMC5455595
Links
Grant list
R35 CA197735 / CA / NCI NIH HHS / United States
R01 CA118553 / CA / NCI NIH HHS / United States
P01 CA087969 / CA / NCI NIH HHS / United States
P30 DK043351 / DK / NIDDK NIH HHS / United States
P01 CA055075 / CA / NCI NIH HHS / United States
R01 CA151993 / CA / NCI NIH HHS / United States
R01 CA137178 / CA / NCI NIH HHS / United States
K24 DK098311 / DK / NIDDK NIH HHS / United States
UM1 CA186107 / CA / NCI NIH HHS / United States
R01 CA169141 / CA / NCI NIH HHS / United States
K07 CA188126 / CA / NCI NIH HHS / United States
UM1 CA167552 / CA / NCI NIH HHS / United States
P50 CA127003 / CA / NCI NIH HHS / United States
K07 CA190673 / CA / NCI NIH HHS / United States