Engineered skin bacteria induce antitumor T cell responses against melanoma

• 成果类型: Article
• 署名作者: Chen, Y. Erin; Bousbaine, Djenet; Veinbachs, Alessandra; Atabakhsh, Katayoon; Dimas, Alex; Yu, Victor K.; Zhao, Aishan; Enright, Nora J.; Nagashima, Kazuki; Belkaid, Yasmine; Fischbach, Michael A.
• 署名单位: Stanford University; Stanford University; Stanford University; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID); National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID); Chan Zuckerberg Initiative (CZI)
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-10074
• DOI: 10.1126/science.abp9563
• 发表日期: 2023-04-13
• 页码: 203-210
• 关键词: immune-responses; immunotherapy; exhaustion; expression; tolerance; resident

摘要

Certain bacterial colonists induce a highly specific T cell response. A hallmark of this encounter is that adaptive immunity develops preemptively, in the absence of an infection. However, the functional properties of colonist-induced T cells are not well defined, limiting our ability to understand anticommensal immunity and harness it therapeutically. We addressed both challenges by engineering the skin bacterium Staphylococcus epidermidis to express tumor antigens anchored to secreted or cell-surface proteins. Upon colonization, engineered S. epidermidis elicits tumor-specific T cells that circulate, infiltrate local and metastatic lesions, and exert cytotoxic activity. Thus, the immune response to a skin colonist can promote cellular immunity at a distal site and can be redirected against a target of therapeutic interest by expressing a target-derived antigen in a commensal.