Abstract LB-250: VISTA expression profile of immune infiltrates and peripheral mononuclear blood cells of non-small cell lung cancer patients
Authors: van der Horst Edward , Chinn Lawrence , Cairns Belinda 
Published: July 2016

Lung cancer is the leading cause of cancer-related deaths in the world. 85% of these cancers are non-small cell lung cancers (NSCLC) and the majority of these patients being diagnosed with advanced disease. Although standard of care initially shows clinical benefit, the overall 5-year survival rate is approximately 4%.

Immunotherapies are emerging as an important treatment option in NSCLC. The most exciting new drugs are checkpoint inhibitors and to date inhibitors against the programmed cell death protein 1 (PD-1/PD-L1) axis have been clinically validated in NSCLC. These agents have been shown to extend survival time with good tolerability in a subset of patients. Nonetheless, there is a need for new immunotherapies and combinations thereof.

Human V-domain Ig suppressor of T cell activation (VISTA aka C10orf54) is a novel broad-spectrum negative checkpoint regulator, which exerts immunosuppressive activities on T-cells. Moreover, genetic and pharmacological intervention of anti-VISTA in combination with anti-PD-1/PD-L1 has shown optimal therapeutic efficacy preclinically. This suggests large potential benefits in a combination therapy of both VISTA and PD-1 blockade1.

VISTA has been shown to be expressed on human hematopoietic cells in normal PBMCs and normal human spleen tissue2. However, no expression analysis of VISTA has been reported in primary NSCLC samples (tissues or PBMCs).

The aim of this study was to a) quantify VISTA expression and define the VISTA positive cells in human tissue samples of NSCLC (both tumor and immune infiltrate) and b) evaluate normal and NSCLC PBMCs by flow cytometry for VISTA positive cell subsets. A total of 200 individual patient tissue samples were evaluated using immunofluorescence based multiplexing for VISTA, CD4, CD8, CD11b, PD-L1 and cytokeratin. Additionally 29 normal and 17 NSCLC PBMCs were evaluated using flow cytometry for VISTA expression with multiple markers.

Our data show that most malignant tumor cells do not express VISTA. However, &gt;90% of the NSCLC sample cores have VISTA positive infiltrating cells. The majority of CD11b positive cells are VISTA positive while some VISTA positive cells are CD11b negative. In general, T cells express low levels of VISTA. Data from PBMCs reveal an up-regulation of VISTA expression in the blood of NSCLC patients that suggest VISTA may have potential as a biomarker. Together these tissue and blood results support VISTA as a promising potential target for immunotherapy intervention in NSCLC either alone or as a combination therapy with PD-1/PD-L1 pathway inhibitors. Igenica's anti-VISTA therapeutic lead antibody IGN-381 is currently in the development stage.

References:

1. Liu J, et al PNAS. 2015; 112 (21): 6682-6687.

2. Lines JL, et al. Cancer Res. 2014; 74 (7): 1924-1932.

Citation Format: Edward van der Horst, Lawrence Chinn, Belinda Cairns. VISTA expression profile of immune infiltrates and peripheral mononuclear blood cells of non-small cell lung cancer patients. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr LB-250.