My laboratory explores how immune cells are impacted by cancer cells, with a particular focus on why the immune system often fails to recognize and eliminate abnormal cells. By understanding the basic mechanisms underlying these failures, we aim to identify new therapeutic targets that will help engage the immune system to provide durable responses to cancer.

A general focus of the laboratory is in understanding how the activation of cytotoxic T cells in the lymph nodes affects 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.

To that end, the Spranger Laboratory is, first, 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 these cancers and contrasting them with immunotherapy-sensitive model systems, we hope to understand why immunotherapy fails to induce protective immunity against these 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, we seek to define tumor cell-intrinsic alterations that either 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 that induces potent anti-viral and anti-tumor immunity. We will also study tumor cell-intrinsic signaling pathways that mediate immune evasion.

Finally, we are studying how the degree of tumor heterogeneity, primarily defined by neo-antigen expression patterns, impairs anti-tumor T cell responses. This is of particular importance as tumors and immune responses co-evolve, and the heterogeneity of the tumor might be also directly influenced by immune responses. Using newly gained mechanistic insights, it is the goal of the group to develop novel therapeutic vaccine strategies that enhance anti-tumor immunity to tumors with heterogeneous antigen expression patterns, and so prevent their metastatic spread.

In addition to being an investigator with the Ludwig Center at MIT, I am an assistant professor of biology at MIT, where I hold the Howard S. and Linda B. Stern Career Development Professorship. I am also a Scholar of the William Guy Forbeck Research Foundation and a Pew-Stewart Scholar for Cancer Research.