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Tumor PDCD1LG2 (PD-L2) expression and the lymphocytic reaction to colorectal cancer
- Publication Year :
- 2017
-
Abstract
- Expression of the immune checkpoint ligand CD274 (programmed cell death 1 ligand 1, PD-L1, from gene CD274) contributes to suppression of antitumor T cell–mediated immune response in various tumor types. However, the role of PDCD1LG2 (PD-L2, CD273, from gene PDCD1LG2) in the tumor microenvironment remains unclear. We hypothesized that tumor PDCD1LG2 expression might be inversely associated with lymphocytic reactions to colorectal cancer. We examined tumor PDCD1LG2 expression by IHC in 823 colon and rectal carcinoma cases within two U.S.-nationwide cohort studies and categorized tumors into quartiles according to the percentage of PDCD1LG2–expressing carcinoma cells. We conducted multivariable ordinal logistic regression analysis to assess the associations of tumor PDCD1LG2 expression with Crohn-like lymphoid reaction, peritumoral lymphocytic reaction, intratumoral periglandular reaction, or tumor-infiltrating lymphocytes, controlling for potential confounders, including microsatellite instability, CpG island methylator phenotype, long-interspersed nucleotide element-1 methylation, and KRAS, BRAF, and PIK3CA mutations. Tumor PDCD1LG2 expression was inversely associated with Crohn-like lymphoid reaction (Ptrend = 0.0003). For a unit increase in the three-tiered ordinal categories of Crohn-like lymphoid reaction, a multivariable OR in the highest (vs. lowest) quartile of the percentage of PDCD1LG2–expressing tumor cells was 0.38 (95% confidence interval, 0.22–0.67). Tumor PDCD1LG2 expression was not associated with peritumoral lymphocytic reaction, intratumoral periglandular reaction, tumor-infiltrating lymphocytes, or patient survival (Ptrend > 0.13). Thus, tumor PDCD1LG2 expression is inversely associated with Crohn-like lymphoid reaction to colorectal cancer, suggesting a possible role of PDCD1LG2-expressing tumor cells in inhibiting the development of tertiary lymphoid tissues during colorectal carcinogenesis. Cancer Immunol Res; 5(11); 1046–55. ©2017 AACR.
- Subjects :
- 0301 basic medicine
Oncology
DNA, Bacterial
Male
Cancer Research
medicine.medical_specialty
Colorectal cancer
Immunology
Tumor M2-PK
Biology
medicine.disease_cause
Article
03 medical and health sciences
0302 clinical medicine
Internal medicine
medicine
Carcinoma
Humans
Lymphocytes
Aged
Tumor microenvironment
Fusobacterium nucleatum
Microsatellite instability
Cancer
Middle Aged
medicine.disease
Programmed Cell Death 1 Ligand 2 Protein
Immune checkpoint
030104 developmental biology
030220 oncology & carcinogenesis
Female
KRAS
Colorectal Neoplasms
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....cec891797ae1370aeb74cc121ca2b87d