What we do
T cells are uniquely gifted immune cells capable of trafficking anywhere in the body and recognizing their target cells with exquisite specificity. They can interact with any given cell as long as it expresses the right antigen. However, we do not know what the final outcome of a given T cell-target cell interaction is for every single cell in our bodies. We do know, however, that some cells such as cancer cells can escape T cell killing while some other cell types are more prone to autoimmunity (e.g. pancreatic beta cells). What are the mechanisms behind these differences? To address this question, we recently generated a new technology called the Jedi mouse (Agudo, Nat. Biotech., 2015). Jedi T cells recognize GFP as their cognate antigen and therefore, can be used in combination with any of the available GFP-expressing mouse lines, cells lines or microorganisms. In the Agudo lab, we are interested in using this platform to study immune surveillance of adult stem cells, cancer stem cells and tumor disseminated cells in order to develop therapeutic strategies for autoimmune diseases and cancer immunotherapy.
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Immune evasion mechanisms of stem cells
Stem cells are responsible for tissue homeostatic replenishment and regeneration upon damage. However, it is still unknown whether these critical cells can escape immune recognition during autoimmune attack, and therefore, can re-grow a damaged tissue once tolerance is restored. Using the Jedi T cells and GFP-reporter mice specifically expressing GFP in several stem cell populations, we found that, most tissue-resident stem cells are susceptible to cellular immunity. However, some stem cells do possess the capacity to escape from both T cell and NK killing (Agudo, Immunity, 2018). Our goal is to investigate the molecular and cellular mechanisms that result in protection of immune privileged stem cells, so we can exploit them in order to develop. |
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Immune surveillance of cancer stem cells
Cancer stem cells or cancer initiating cells are a subpopulation of rare cancer cells that have the capability of self-renewing and the potential to grow a new full-fledged tumor mass. Such cells are hypothesized to persist in tumors as a distinct population and cause relapse and metastasis by giving rise to new tumors. Therefore, development of specific therapies targeted at CSCs holds hope for improvement of survival and quality of life of cancer patients, especially for patients with high risk of developing metastatic disease.
Cancer stem cells or cancer initiating cells are a subpopulation of rare cancer cells that have the capability of self-renewing and the potential to grow a new full-fledged tumor mass. Such cells are hypothesized to persist in tumors as a distinct population and cause relapse and metastasis by giving rise to new tumors. Therefore, development of specific therapies targeted at CSCs holds hope for improvement of survival and quality of life of cancer patients, especially for patients with high risk of developing metastatic disease.
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Immune escape mechanisms of dormant and metastatic stem cells
Most cancer patients do not die due to the primary tumor but as the result of metastasis. Metastases arise from cells that can escape the primary tumor and colonize other tissues. We aim to understand how these cells escape immune recognition outside the immune suppressive microenvironment of the primary tumor. We take advantage of fluorescent GFP tumor cells to facility their detection and measurement and out unique Jedi T cells as an invaluable tool to interrogate how antigen-specific T cells interact with these rare (and yet, dangerous) tumor cells. The outcome of these studies will have deep implications in cancer immunotherapy as, targeting of these cells will prevent recurrence of metastatic disease. |