Abstract 43P
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.
Resources from the same session
147P - Pre-clinical evaluation and safety profile of the highly selective anti-VISTA antibody K01401-020
Presenter: Geneviève Gueguen Dorbes
Session: Poster Display
148P - HexaBody-OX40, a novel Fc_ receptor crosslinking-independent OX40-targeting antibody, exhibits agonistic activity in vitro and antitumor activity in vivo
Presenter: Kristel Kemper
Session: Poster Display
149P - HLA/SIRPa bispecifics-A novel multitarget therapeutic strategy to induce potent anti-tumor immune responses
Presenter: anahita rafiei
Session: Poster Display
150P - Chemotherapy in combination with Toll-like receptor agonism promoted antitumor immune response in triple negative breast cancer
Presenter: Eunice Dotse
Session: Poster Display
151P - Tumor organoid-derived TIL therapy for colorectal cancer
Presenter: Marc Leushacke
Session: Poster Display
152P - Discovery of best-in-class dual-acting A2AR/A2BR antagonists that are functional in high adenosine environment
Presenter: Nainesh Katagihallimath
Session: Poster Display
153P - Discovery of a Novel, Dual CD73 and PD-1 Targeting Multispecific Drug Fc-Conjugate (DFC) for the Treatment of Cancer
Presenter: James Levin
Session: Poster Display
154P - Computer-aided drug design based on CLDN4 ligand and its biological evaluation in ovarian cancer
Presenter: Yi Xu
Session: Poster Display
155P - A Phase 1 Study Exploring the Safety and Tolerability of the Small-Molecule PD-L1 Inhibitor INCB099280 in Select Advanced Solid Tumors
Presenter: Hans Prenen
Session: Poster Display
156TiP - The LUNGVAC-study; A randomized phase II, open-label, multicenter study investigating efficacy and safety of anti-PD-1/PD-L1 treatment +/- UV1 vaccination as first line treatment in patients with inoperable advanced or metastatic non-small cell lung cancer (NSCLC)
Presenter: Elin Marie Stensland
Session: Poster Display