Xinna Zhang, Ph.D. – VAI Seminar Series

Targeting antigen presentation to overcome immune evasion in breast cancer

Speaker Information

Xinna Zhang, Ph.D.
Assistant Professor
Medical and Molecular Genetics
Indiana University School of Medicine

• Abstract/Bio: Breast cancer is a major clinical challenge in women due to genetic heterogeneity and lack of actionable targets. Despite recent approval of immune checkpoint blockade (ICB) therapy for advanced or metastatic triple-negative breast cancer (TNBC), only modest response rates have been achieved in a small number of patients with breast cancer. Immune evasion is a pivotal event in tumor progression. To eliminate human cancer cells, current immune checkpoint therapy is set to boost the CD8+ T cell mediated cytotoxicity. However, this action is eventually dependent on the efficient recognition of tumor-specific antigens via T cell receptors. One primary mechanism by which tumor cells evade immune surveillance is to downregulate their antigen presentation. Little progress has been made toward harnessing potential therapeutic targets for enhancing antigen presentation on the tumor cell. Here, we identified MAL2 as a key player that determines the turnover of the antigen-loaded MHC-I complex and reduces the antigen presentation on tumor cells. In preclinical models, depletion of MAL2 in breast tumor cells profoundly enhanced the cytotoxicity of tumor-infiltrating CD8+ T cells and suppressed breast tumor growth, suggesting that MAL2 is a potential therapeutic target for breast cancer immunotherapy.
• Host: Hong Wen, Ph.D.