Cancer immunotherapy targets immune-regulatory signal molecules such as the programed cell death receptor ligand PD-L1 and cytotoxic T lymphocyte antigen CTLA4. Clinical trials have shown encouraging outcomes including, durable responses first seen in melanoma. However, a small subset of patients do not respond.
With the success of these therapies and the deeper understanding of the immune-system and its regulation in the context of cancer, more and more potential immune-regulatory molecules are being discovered and examined. We recently discovered one of these molecules following a high-throughput screen for novel tumor antigens in melanoma in collaboration with CSL Limited. The screening outcome led to the discovery of a protein belonging to the Butyrophylin (BTN) family on the surface of melanoma cells called BTN2A1. BTN2A1 shares sequence and structure similarity to the B7 family of immune-regulatory molecules, which include Btnl2 and Skint1 in mice.
The purpose of this project is to validate preliminary findings of BTN2A1 expression in melanoma. BTN2A1 was found to be highly membrane-expressed in 8/10 melanomas tested. Multiplex fluorescent immunohistochemical staining with the VECTRA (Perkin Elmer®) enables staining of multiple targets. This will allow us to understand the expression pattern and spatial relationship of different immune-regulatory molecules such as BTN2A1 and PD-L1 within the same tumor context.
The distribution of BTN2A1 in melanoma, pancreatic adenocarcinoma, hepatocellular carcinoma, breast and prostate cancer have been evaluated and compared with the expression patterns in normal counterpart tissues are presented in this study. We have found that BTN2A1 are generally more highly expressed in cancer cells in comparison to their normal counterparts.