Back to Search
Start Over
The clinical significance of PD-L1 in advanced gastric cancer is dependent on ARID1A mutations and ATM expression.
- Source :
- OncoImmunology; Aug2018, Vol. 7 Issue 8, p1-1, 1p
- Publication Year :
- 2018
-
Abstract
- Whether PD-L1 expression is associated with survival outcomes in gastric cancer (GC) is controversial. The inhibition of the PD-1/PD-L1 pathway is effective against genomically unstable tumors. Hypothesizing that also the clinical significance of PD-L1 might be dependent on the activation of molecular circuits ensuring genomic stability, we evaluated PD-L1 expression in tissue samples from 72 advanced GC patients treated with first-line chemotherapy. Samples were already characterized for DNA damage repair (DDR) component expression (pATM, pChk1, pWee1, γ-H2AX and pRPA2) along with mutations in DDR-linked genes (TP53 and ARID1A). Overall, PD-L1 expression was not associated with progression-free survival (PFS) and overall survival (OS), independently on whether we considered its expression in tumor cells (PD-L1-TCs) or in the immune infiltrate (PD-L1-TILs). In subgroup analysis, positive PD-L1-TC immunostaining was associated with better PFS in patients whose tumors did not carry DDR activation (multivariate Cox: HR 0.34, 95%CI: 0.15-0.76, p = 0.008). This subset (DDR<superscript>off</superscript>) was characterized by negative pATM expression or the presence of ARID1A mutations. Conversely, the relationship between PD-L1-TC expression and PFS was lost in a molecular scenario denoting DDR activation (DDR<superscript>on</superscript>), as defined by concomitant pATM expression and ARID1A wild-type form. Surprisingly, while PD-L1-TC expression was associated with better OS in the DDR<superscript>off</superscript> subset (multivariate Cox: HR 0.41, 95% CI: 0.17-0.96, p = 0.039), in the DDR<superscript>on</superscript> subgroup we observed an opposite impact on OS (multivariate Cox: HR 2.56, 95%CI: 1.06-6.16, p = 0.036). Thus, PD-L1-TC expression may impact survival outcomes in GC on the basis of the activation/inactivation of genome-safeguarding pathways. [ABSTRACT FROM AUTHOR]
- Subjects :
- CANCER
TUMORS
GENOMICS
CANCER chemotherapy
DNA
Subjects
Details
- Language :
- English
- ISSN :
- 21624011
- Volume :
- 7
- Issue :
- 8
- Database :
- Complementary Index
- Journal :
- OncoImmunology
- Publication Type :
- Academic Journal
- Accession number :
- 131687922
- Full Text :
- https://doi.org/10.1080/2162402X.2018.1457602