The Joshi Lab uses intricate tumor models and advanced approaches to investigate immune cell interactions with developing tumors.
How effector T cells differentiate during cancer development and infection
Understanding mechanisms and maintenance of peripheral T cell tolerance
Understanding how T cells shape the cancer development and progression
Developing advanced animal models to recapitulate human disease
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Understanding mechanisms of action for T cells in cancer and health
Learn more about the published work from the lab on T cell differentiation and tolerance mechanisms
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A focus on structure
KP-NINJA tumor with associated B (red) and T (yellow) cell
Immune responses benefit from organization. Secondary lymphoid tissues (SLOs) provide this by both recruiting adaptive and innate immune cells and facilitating their interactions. This allows for the initiation of T cell responses, but also for the maintenance of T cell populations through the provisions of critical cytokines, like IL-7. By contrast, it is the disruption of the normal architecture that is thought to impair immune responses against chronic viral infections such as Clone 13 LCMV infection.
In peripheral tissues, tertiary lymphoid structures (TLS) are thought to serve many of the same putative functions as SLOs, but less is known about these structures. Recent work has highlighted that TLS are frequently associated with cancer across many types, and their presence correlates with better outcomes and responses to immunotherapy. However, what theses structures do remains unclear.
We previously reported that TLS form in the KP lung adenocarcinoma model, and that these structures can recruit anti-tumor T cells and facilitate their interactions with tumor antigen-presenting dendritic cells (Joshi Immunity 2015). Moreover, depletion of regulatory T cells (Tregs) in TLS unleashed a potent anti-tumor immune response that led to destruction of the tumor. The lab is currently combining our novel models with advanced imaging techniques to understand how TLS form and what the role of tumor antigens are in this process.
This work is part of an ongoing collaborative effort funded via a Mark Foundation Endeavor Grant
The Joshi lab is a diverse group of scientists that are passionate about understanding the science of T cells and cancer.
