Impact of the immune-checkpoint HLA-G/ILT4 on the expression of VEGF in clear cell renal cell carcinoma.

GARCIA MARCELA; PALMA MARÍA BELÉN; VERINE JEROME; MIRIUKA SANTIAGO; INDA ANA MARIA; ERRECALDE ANA LÍA; DESGRANDSCHAMPS FRANCOIS; CAROSELLA EDGARDO; TRONIK LE-ROUX DIANA

Paris

Congreso; 8th International Conference on HLA-G; 2019

CEA, Service de Recherches en Hemato-Immunologie. Institut Universitaire d'Hematologie- Hopital Saint Louis.

Clear cell renal cell carcinoma (ccRCC), one of the most aggressive renal cancer, is characterizedby early lymph node metastasis and bad prognosis. Most therapies targeting advanced ormetastatic ccRCC are based, as first-line treatment, on the administration of the vascularendothelial growth factor (VEGF) neutralizing antibody termed Bevacizumab. Despite provenbenefits, the expected results were not obtained for the majority of patients, implying that noveltherapeutic views have to be developed. In this context, the aim of our work was to determinewhether an interplay between angiogenesis and immune-checkpoints could constitute apromising new therapeutic opportunity. To this end, we have simultaneously evaluate tumorangiogenesis, based on the analysis of the expression levels of VEGF and the endothelial antigenCD34 and the immune checkpoint HLA-G/ILT4. Our results show that VEGF is highly expressedin most ccRCC samples, which confirms that these are highly vascularized tumors. The immunecheckpoint HLA-G/ILT4 was also highly expressed in these tumors. In addition, ILT4, the HLA-Greceptor, was detected in the macrophages surrounding tumor cells, suggesting the generationof an immune-tolerant microenvironment that might favor tumorigenesis. Notably, semiquantitative RT-PCR analysis provided the first evidence on the transcriptional relationshipbetween the HLA-G/ILT4 and the VEGF family. Namely, the expression of HLA-G and ILT4decreases the levels of VEGF-A whereas those of VEGF-C are increased. We believe thatsimultaneously engaging VEGF and HLA-G blockade would constitute a promising newtherapeutic opportunity.