B7-H1 Expression Is Associated with Poor Prognosis in Colorectal Carcinoma and Regulates the Proliferation and Invasion of HCT116 Colorectal Cancer Cells

Shi, Shengjia; Wang, Lijuan; Wang, Guodong; Z, Guo; Wei, Ming; Meng, Yanyan; Yang, An‐Gang; Wen, Weihong

doi:10.1371/journal.pone.0076012

Cited by 157 publications

(117 citation statements)

References 37 publications

Supporting

Mentioning

108

Contrasting

Unclassified

Order By: Relevance

“…Multivariate analysis showed that PD-L1/PD-L2 mRNA overexpression was an independent prognostic factor negatively influencing the prognosis of patients with CRC. Thus, our results demonstrate PD-L gene overexpression as an independent prognostic factor in CRC and confirm clinical data in solid tumors [30][31][32][33]. Consequently, PD-L expression is suggestive to be involved in downregulating anti-tumor immunity and thus promoting further tumor growth and metastasis in patients with CRC.…”

Section: Discussionsupporting

confidence: 85%

See 1 more Smart Citation

Clinical Significance and Therapeutic Potential of the Programmed Death Ligand-1 (PD-L1) and PD-L2 Expression in Human Colorectal Cancer

Gasser¹,

Koenigshausen²,

Grimm³

et al. 2017

J Cancer Sci Ther

View full text Add to dashboard Cite

Purpose: The programmed death-1/programmed death ligand (PD-1/PD-L) pathway in T cell activation has been shown to play an important role in tumor evasion from host immunity. The predictive value of PD-L1 and PD-L2 expression in colorectal cancer (CRC) remains still under discussion. We analyzed whether negative signaling of infiltrating PD-1-positive T cells through PD-L1 and PD-L2 within the tumor could promote further tumor progression through downregulation of anti-tumor immunity. Methods:We investigated PD-L1 and PD-L2 expression in tumors from patients with CRC and analyzed its prognostic significance with respect to outcome analysis. Conclusion:The presented results from primary tumors and CRC patient outcome analysis suggest that negative signaling of infiltrating PD-1-positive T cells through PD-L1 expression within the tumor may promote further tumor progression through downregulation of anti-tumor immunity. Co-expression of PD-1 on CD4/Foxp3-positive T cells was found indicating T regulatory cell-mediated mechanisms by which tumor cells can evade immune recognition and destruction. This study demonstrates the importance of strategies inhibiting negative PD-1/ PD-L1 signaling in CRC.

show abstract

Section: Discussionsupporting

confidence: 85%

“…However, PD-L1 expression in CRC has not been fully addressed so far. Nevertheless, a strong correlation between PD-L1 expression on tumor cells and discrepant clinical outcomes has been observed [30,33]. Thus, the predictive value of PD-L1 expression on tumor cells is still controversial in CRC patients.…”

Section: Discussionmentioning

confidence: 99%

Clinical Significance and Therapeutic Potential of the Programmed Death Ligand-1 (PD-L1) and PD-L2 Expression in Human Colorectal Cancer

Gasser¹,

Koenigshausen²,

Grimm³

et al. 2017

J Cancer Sci Ther

View full text Add to dashboard Cite

show abstract

“…Similar to myeloma cells, B7-H1 knockdown in pancreatic cancer cell lines increased susceptibility to chemotherapy and inhibited cell proliferation (33,34). In a colorectal cancer cell line, silencing of B7-H1 with short interfering RNA (siRNA) inhibited cell growth, migration, and invasion and increased spontaneous apoptosis (14). Thus, B7-H1 molecules not only on myeloma cells but also on cells of various other tumors may be directly associated with aggressive behavior.…”

Section: Discussionmentioning

confidence: 99%

“…The impact of tumorassociated B7-H1 expression on prognosis has been reported in cancer patients. Overall survival rates are significantly lower in patients with high B7-H1 expression compared with those with low B7-H1 expression in some tumors (14)(15)(16)(17). Abundant PD-1 on tumor-infiltrating T cells is also associated with poor overall survival (6,18,19).…”

Section: Introductionmentioning

confidence: 99%

Myeloma Drug Resistance Induced by Binding of Myeloma B7-H1 (PD-L1) to PD-1

Ishibashi

Tamura

Sunakawa

et al. 2016

Cancer Immunology Research

View full text Add to dashboard Cite

B7 homolog 1 (B7-H1)-expressing myeloma cells not only inhibit myeloma-specific cytotoxic T lymphocytes (CTL), but also confer a proliferative advantage: resistance to antimyeloma chemotherapy. However, it remains unknown whether B7-H1 expressed on myeloma cells induces cellular responses associated with aggressive myeloma behaviors. To address this question, we analyzed the proliferation and drug sensitivity of B7-H1-expressing myeloma cells transfected with B7-H1-specific short-hairpin RNA or treated with programmed cell death (PD)-1-Fc-coupled beads. Knockdown of B7-H1 expression in myeloma cells significantly inhibited cell proliferation and increased apoptosis induced by the chemotherapeutic alkylating agent melphalan, with downregulation of the expression of cell cycle-related genes (CCND3 and CDK6) and antiapoptotic genes (BCL2 and MCL1). B7-H1 molecules thus contributed to myeloma cell-cycle progression and suppression of drug-induced apoptosis. B7-H1-expressing myeloma cells had a higher affinity for PD-1 than for CD80. PD-1-Fc beadtreated myeloma cells also became resistant to apoptosis that was induced by melphalan and the proteasome inhibitor bortezomib. Apoptosis resistance was associated with the PI3K/AKT pathway. Both myeloma cell drug resistance and antiapoptotic responses occurred through the PI3K/AKT signaling pathway, initiated from "reverse" stimulation of B7-H1 by PD-1. Therefore, B7-H1 itself may function as an oncogenic protein in myeloma cells. The interaction between B7-H1 on myeloma cells and PD-1 molecules not only inhibits tumorspecific CTLs but also induces drug resistance in myeloma cells through the PI3K/AKT signaling pathway. These observations provide mechanistic insights into potential immunotherapeutic benefits of blocking the B7-H1-PD-1 pathway.

show abstract

“…In contrast, two previous studies reported PD-L1 expression in tumor cells to be an independent predictor of poor prognosis in CRC. 9,10 Data on the epigenetic regulation of the PD-L1 encoding gene CD274 are sparse. Pharmacologically induced gene methylation, however, has been shown to adjust PD-L1 expression in various malignancies.…”

Section: Introductionmentioning

confidence: 99%

PD-L1 (CD274) promoter methylation predicts survival in colorectal cancer patients

et al. 2016

View full text Add to dashboard Cite

This study evaluates promoter methylation of the programmed cell death ligand 1 (PD-L1) as a biomarker in a cohort of 383 colorectal cancer patients. PD-L1 methylation (mPD-L1) was inversely correlated with PD-L1 mRNA expression (p D 0.001) and was associated with significantly shorter overall survival (OS, p D 0.003) and recurrence-free survival (RFS, p < 0.001). In age-stratified multivariate Cox proportional hazards analyses including sex, tumor, nodal, distant metastasis categories, microsatellite instability (MSI)-status, and PD-L1 mRNA, mPD-L1 is classified as an independent prognostic factor (OS: p D 0.030; RFS: p < 0.001). Further studies are needed to evaluate PD-L1 methylation as a biomarker for response prediction of immunotherapies targeting the PD-1/PD-L1 axis.

show abstract

B7-H1 Expression Is Associated with Poor Prognosis in Colorectal Carcinoma and Regulates the Proliferation and Invasion of HCT116 Colorectal Cancer Cells

Cited by 157 publications

References 37 publications

Clinical Significance and Therapeutic Potential of the Programmed Death Ligand-1 (PD-L1) and PD-L2 Expression in Human Colorectal Cancer

Clinical Significance and Therapeutic Potential of the Programmed Death Ligand-1 (PD-L1) and PD-L2 Expression in Human Colorectal Cancer

Myeloma Drug Resistance Induced by Binding of Myeloma B7-H1 (PD-L1) to PD-1

PD-L1 (CD274) promoter methylation predicts survival in colorectal cancer patients

Contact Info

Product

Resources

About