Evaluation of cancer-testis antigens as immunotherapeutic targets for sarcoma
Anna Jirovec1,2, Fanny Tzelepis1, Joel Werier1, Jean-Simon Diallo1,2 1Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada; 2Centre for innovative Cancer Research, Ottawa Hospital Research Institute, Ottawa, ON, Canada
T-cell based cancer immunotherapies are a promising alternative to traditional cancer treatments due to their ability to direct the immune system to eliminate cancer cells, leaving healthy cells unharmed. Our lab aims to develop a T cell based immunotherapy for sarcoma. The development of this immunotherapy requires the identification of a targetable immunogenic sarcoma antigen. Cancer-testis antigens (CTA) are a group of highly immunogenic tumor-associated proteins that may serve as antigens for CD8+ T-cell recognition. Other parameters such as ability of antigen-specific T cells to infiltrate sarcoma tumors, immune suppression, and expression of HLA-peptide complex on the surface of cancer cells, which is crucial for recognition of tumor cells by CD8+ T cells, also play important roles in the outcome of the therapy. Evaluation of these parameters will be important for the design and outcome of our immunotherapy. The goal of this study is to screen for CTA expression, HLA expression and tumor T-cell infiltration in human sarcoma samples by immunohistochemistry (IHC). We evaluated the expression NY-ESO-1, MAGE-A3, SSX and survivin in human sarcoma samples to identify which antigen is most commonly expressed, as well as which is the most highly expressed. Quantification of IHC staining for CTAs revealed positive expression in 78.5% of samples. MAGE-A3, SSX and survivin are expressed at intermediate to very high levels. Contrastingly, NY-ESO-1 is expressed at low levels in the 60% of sarcoma samples. Additionally, evaluation of HLA staining confirmed HLA expression in all sarcoma samples. CD3 staining revealed tumor T-cell infiltration in over 70% of sarcoma samples. High expression of MAGE-A3, SSX and survivin in sarcoma samples indicates that these CTAs could be used as immunotherapeutic targets. HLA expression and tumor T-cell infiltration in sarcoma samples suggests that CD8+ T-cells generated in response to an immunotherapy will effectively infiltrate tumor and recognize HLA-antigen complexes on tumor cells. These results will contribute to the development of an immunotherapy for sarcoma.
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