Clinical Significance and Therapeutic Potential of the Programmed DeathLigand-1 (PD-L1) and PD-L2 Expression in Human Colorectal Cancer
2017
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 PDL2
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.
Results: T cell infiltration was observed in 90.5% of the tumors, with 58% of the patients demonstrating PD-1-
positive T cells in their tumors. Patients who developed PD-1-positive T cell infiltration showed increased PD-L1-
expression within their tumors than PD-1-T cell negative individuals. Presence of tumor infiltrating PD-1-positive T
cells was more pronounced in advanced stage cancers than in early cancers. Ligand expression (PD-L1/PD-L2) in
the tumors combined with dense PD-1-positive T cell infiltration was associated with poor prognosis. Multivariate
analysis demonstrated that PD-L expression in the tumors was an independent prognostic factor in CRC.
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.
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