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The Spranger Laboratory is working to understand how immune cells are impacted by cancer cells and particularly focuses on when the immune system fails to recognize and eliminate abnormal cells. By understanding these basic immunological mechanisms, the group aims to identify new therapeutic targets, which will engage the immune system to provide durable responses to cancer. A general focus of the Laboratory is in understanding how the cytotoxic T cell activation in the lymph node affect the quality and durability of the anti-tumor T cell response. Understanding the factors required to induce a systemic and long-lasting anti-tumor immune response will enable us to fight and prevent metastatic cancer spread.

First, the Spranger Laboratory is working to determine whether tissue-site specific immune responses determine the sensitivity to immunotherapies such as checkpoint blockade therapy. To do so we have established models of orthotopic lung and colon cancer as well as metastatic ovarian cancer. By carefully characterizing the immune responses to any of these cancers and contrasting them with immunotherapy sensitive model system we aim to understand why immunotherapy fails to induce protective immunity in this set of cancers. While our primary emphasis is on cytotoxic T cell responses we will also study the tissue specific myeloid compartment and its impact on activation of T cells.

Second, the group seeks to define tumor cell-intrinsic alterations which induce or prevent anti-tumor immunity in carcinomas. To achieve this, we will focus on immune potentiation factors, such as tumor cell-derived type-I interferon, a natural alarmin which induces potent anti-viral and anti-tumor immunity. But we will also study tumor cell-intrinsic signaling pathways mediated immune evasion.

Finally, the Spranger Laboratory is aiming to understand how the degree of tumor heterogeneity, primarily defined by neo-antigen expression patterns, is impairing anti-tumor T cell responses. This is of particular importance as tumors and immune responses co-evolve and heterogeneity of the tumor might be also directly impacted by immune responses. Using the newly gained mechanistic insights it is the goal of the group to develop novel therapeutic vaccine strategies which would enhance anti-tumor immunity to tumors with heterogeneous antigen expression patterns and thus prevent metastatic spread.

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