Back to Search
Start Over
Increased CD8 Tumor Infiltrating Lymphocytes in Colorectal Cancer Microenvironment Supports an Adaptive Immune Resistance Mechanism of PD-L1 Expression.
- Source :
-
Asian Pacific journal of cancer prevention : APJCP [Asian Pac J Cancer Prev] 2019 Nov 01; Vol. 20 (11), pp. 3421-3427. Date of Electronic Publication: 2019 Nov 01. - Publication Year :
- 2019
-
Abstract
- Background: Tumor cells express programmed death ligand-1 (PD-L1) through several biological processes, thereby having different clinical significance depending on the underlying mechanism of expression. Currently, mechanisms leading to PDL1 gene expression in colorectal cancer (CRC) are not fully understood.<br />Methods: We investigated 98 Indonesia CRC patients to determine PD-L1 protein expressions and their correlations with PD-L1 gene copy number status, tumor infiltrating lymphocytes (TILs), tumor mutational profile, as well as clinicopathologic features.<br />Results: Our investigation demonstrated that 18% of patients positively expressed PD-L1. Further analysis on PD-L1 copy number revealed that all PD-L1+ tumors had normal copy number, indicating that the expression of PD-L1 was not a consequence of genetic amplification of PD-L1. From TILs analysis, there was a significant increase of CD8 in all tumor cells expressing PD-L1 (P=0.0051), indicating that the inducible PD-L1 expression was the prominent mechanism occurred in CRC. Furthermore, the expression of PD-L1 in this CRC population was significantly associated with high frequency of MSI compared to the remainder PD-L1- tumors (P=0.0001), suggesting the natural immunogenicity of tumors via MSI status plays role in attracting immune response. On the other hand, p53 mutations which were frequently observed within Indonesian CRCs (76.5%), they were not associated with PD-L1 expression (p=0.1108), as well as KRAS gene (29.6%; p=0.5772) and BRAF gene mutations (5%; p=0.2171).<br />Conclusion: Our study demonstrated that PD-L1 expressions in CRC were predominantly found as a consequence of infiltrating CD8 T lymphocytes that in part arise in the setting of microsatellite instability. Taken together, our findings further support the role of adaptive immune resistance to drive PD-L1 induction in tumor microenvironment and may provide important rationale for strategy implementation of immunotherapy for CRC cases.<br />.
- Subjects :
- Adaptive Immunity genetics
Adolescent
Adult
Aged
Aged, 80 and over
Child
Colorectal Neoplasms genetics
Female
Gene Dosage genetics
Gene Dosage immunology
Humans
Indonesia
Male
Microsatellite Instability
Middle Aged
Mutation genetics
Mutation immunology
Tumor Microenvironment genetics
Young Adult
Adaptive Immunity immunology
B7-H1 Antigen immunology
CD8-Positive T-Lymphocytes immunology
Colorectal Neoplasms immunology
Lymphocytes, Tumor-Infiltrating immunology
Tumor Microenvironment immunology
Subjects
Details
- Language :
- English
- ISSN :
- 2476-762X
- Volume :
- 20
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Asian Pacific journal of cancer prevention : APJCP
- Publication Type :
- Academic Journal
- Accession number :
- 31759368
- Full Text :
- https://doi.org/10.31557/APJCP.2019.20.11.3421