43P - Immune and tumor cells expression of VISTA in a panel of cancer indications: A strategy to inform selection of patients treated with anti-VISTA

Background

V-domain Ig suppressor of T-cell activation (VISTA) is a B7 family member that acts as an immune checkpoint regulator. VISTA is expressed in various cell subtypes such as tumor, myeloid, lymphoid, and endothelial cells. Within the tumor microenvironment (TME), its expression on myeloid cells favors immunosuppressive conditions and prevents T cell recruitment into tumors. In patients, high VISTA expression is associated with poor prognosis in multiple tumor indications, and act as a mediator of resistance to immune checkpoint therapies. Thus, VISTA appears as a potential therapeutic target in oncology requiring a more detailed characterization of its expression pattern across tumor indications to eventually inform future patient selection.

Methods

In tissue microarrays (TMAs) covering 23 solid tumor indications and representing more than 1000 patients, we investigated the expression of VISTA in combination with different immune and tumor cells markers. For this purpose, we developed and validated a 7-color multiplex immunofluorescence protocol to quantify VISTA expression on tumor cells (Cytokeratin/Melan A), cytotoxic CD8 T cells (CD8), myeloid cells (CD33), M2 macrophages (CD163), and PD-L1 positive cells (PD-L1).

Results

Consistent with the literature, we have observed that VISTA is not only predominantly expressed in the TME but also frequently and highly expressed in tumor cells in some indications such as sarcoma, mesothelioma, kidney, and gastric cancer for example. In the TME, VISTA is found to be highly expressed in CD33 and CD163 populations, particularly in kidney cancer and sarcoma. Moreover, we found that tumor infiltrating CD8 T-cells often expressed VISTA, notably in sarcoma, kidney cancer, and hepatocellular carcinoma.

Conclusions

Finally, we propose indications of interest that may support patient selection strategy for the development of anti-VISTA treatments.

Legal entity responsible for the study

Pierre Fabre Laboratories.

Funding

Pierre Fabre Laboratories.

Disclosure

P. Launay, A. Pillon, R. Bonnet, D. Vinet, A. Alloy, L. Lacastaigneratte, C. Welsch, C. Larzabal, G. Zorza, G. Gueguen Dorbes, O. Geneste, F. Hofmann, M-O. Roy: Financial Interests, Personal, Full or part-time Employment: Pierre Fabre.