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Bruno Silva-Santos Lab
Major Interests
T lymphocytes play crucial roles in cellular immunity against pathogens and tumors. However, T lymphocytes can also be a major cause of autoimmunity and allergy. These (patho)physiological roles of T lymphocytes depend on their cellular and molecular activities, namely the production of cytotoxic molecules and pro- versus anti-inflammatory cytokines. In our Lab we employ in vitro and in vivo models to study the differentiation, activation and expansion (in response to infections or tumors) of murine and human T lymphocytes.
We have previously demonstrated that the development of important T lymphocyte subsets, namely gamma-delta (γδ) T cells and regulatory T cells, is orchestrated by molecular events taking place in the thymus that are highly dependent on interactions between the receptor CD27 (expressed on T cell progenitors) and its ligand CD70 (mostly present on thymic epithelial cells). Moreover, the CD27/CD70 signaling pathway is also critical for the expansion of γδ T cells in the periphery, which may be exploited in future cancer immunotherapy protocols. In this context, we have also identified novel molecular determinants of tumor cell recognition by human gamma-delta T cells, which unexpectedly are based on natural killer (NK) receptors such as NKG2D or NKp30. In the future we plan to further dissect the molecular pathways that control γδ T cell activation and tumor cell recognition. Most importantly, we aim to apply our knowledge on γδ T cells to the pre-clinical and clinical targeting of acute and chronic leukemias. Given that the major therapeutic hurdle following conventional chemotherapy consists of leukemia relapse, we will explore the possibility of using immune intervention (based on γδ T cells) to target escape variants and thus prevent cancer relapse.

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