Clinical Significance and Therapeutic Potential of the Programmed Death Ligand-1 (PD-L1) and PD-L2 Expression in Human Colorectal Cancer
| Autor: | Martin Gasser, Matthias Koenigshausen, Christoph-Thomas Germer, Melissa Y. Yeung, Martin Wagner, raker, Uwe Heemann, Roberta Rehder, Anil Ch, Ekaterina Nichiporuk Stumpf, Sudipta Tripathi, Uwe Maeder, Carmen Australia Paredes Marcondes Ribas, Tanja Grimmig, Ana Maria Waaga-Gasser, Claudia Stein, Roman Moench, Martin Grimm |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Cancer Research biology business.industry Colorectal cancer medicine.medical_treatment T cell Cell FOXP3 Immunotherapy medicine.disease 03 medical and health sciences 030104 developmental biology medicine.anatomical_structure Oncology Downregulation and upregulation Tumor progression PD-L1 Immunology medicine Cancer research biology.protein business |
| Zdroj: | Journal of Cancer Science & Therapy. |
| ISSN: | 1948-5956 |
| DOI: | 10.4172/1948-5956.1000475 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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