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Prognostic Value of PD-L1, PD-1 and CD8A in Canine Diffuse Large B-Cell Lymphoma Detected by RNAscope
- Source :
- Veterinary Sciences, Vol 8, Iss 120, p 120 (2021), Veterinary Sciences, Veterinary Sciences; Volume 8; Issue 7; Pages: 120
- Publication Year :
- 2021
- Publisher :
- MDPI AG, 2021.
-
Abstract
- Immune checkpoints are a set of molecules dysregulated in several human and canine cancers and aberrations of the PD-1/PD-L1 axis are often correlated with a worse prognosis. To gain an insight into the role of immune checkpoints in canine diffuse large B-cell lymphoma (cDLBCL), we investigated PD-L1, PD-1 and CD8A expression by RNAscope. Results were correlated with several clinico-pathological features, including treatment, Ki67 index and outcome. A total of 33 dogs treated with chemotherapy (n = 12) or chemoimmunotherapy with APAVAC (n = 21) were included. PD-L1 signal was diffusely distributed among neoplastic cells, whereas PD-1 and CD8A were localized in tumor infiltrating lymphocytes. However, PD-1 mRNA was also retrieved in tumor cells. An association between PD-L1 and PD-1 scores was identified and a higher risk of relapse and lymphoma-related death was found in dogs treated with chemotherapy alone and dogs with higher PD-L1 and PD-1 scores. The correlation between PD-L1 and PD-1 is in line with the mechanism of immune checkpoints in cancers, where neoplastic cells overexpress PD-L1 that, in turn, binds PD-1 receptors in activated TIL. We also found that Ki67 index was significantly increased in dogs with the highest PD-L1 and PD-1 scores, indirectly suggesting a role in promoting tumor proliferation. Finally, even if the biological consequence of PD-1+ tumor cells is unknown, our findings suggest that PD-1 intrinsic expression in cDLBCL might contribute to tumor growth escaping adaptive immunity.
- Subjects :
- PD-L1
040301 veterinary sciences
Veterinary medicine
diffuse large B-cell lymphoma
Article
0403 veterinary science
03 medical and health sciences
Immune system
Chemoimmunotherapy
PD-1
SF600-1100
Medicine
Receptor
RNAscope
030304 developmental biology
0303 health sciences
General Veterinary
biology
business.industry
Tumor-infiltrating lymphocytes
allergology
04 agricultural and veterinary sciences
Acquired immune system
medicine.disease
Lymphoma
dog
biology.protein
Cancer research
business
Diffuse large B-cell lymphoma
Subjects
Details
- Language :
- English
- ISSN :
- 23067381
- Volume :
- 8
- Issue :
- 120
- Database :
- OpenAIRE
- Journal :
- Veterinary Sciences
- Accession number :
- edsair.doi.dedup.....ef0134f270ed73de3e0c1aea082942a2