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Ricardo Fernandes

COI Group Leader

Cancer Immunology - T cell signalling

Tumor immune surveillance, whereby the immune system identifies and targets cancerous cells, plays a major role in eliminating tumors. The main objective of my group research is to identify key functional aspects affecting anti-tumor responses by T cells. Our research is broadly split in two complementary areas:

-        Identification of potent peptide antigens that drive robust T cell activation against tumor cells;

-        Modulation of immune receptor signaling with a focus on “immune checkpoint receptors” in order to potentiate T cell effector functions.

Continuous exposure to tumor antigens gives rise to an “exhausted” phenotype, in which immune cells become less responsive and, ultimately, fail to control tumor growth. T cell exhaustion is characterized by changes in gene expression, including the up-regulation of cell surface receptors, such as the programmed cell death protein 1 (PD-1) and the cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), among many others. Continuous signaling by these immune checkpoint receptors gradually “shuts down” the immune response. We have recently developed new protein molecules to regulate the activity of key surface receptors in order to enhance T cell function. Furthermore, tumors often present mimotopes, altered peptide antigens, which T cells recognize and respond to. However, mimotopes often elicit weak T cell activation. Currently, there is a paucity of methods to identify robust peptide antigens recognized by T cells. Our group develops new approaches to deorphanize T-cell receptors (TCR) of interest, namely those involved in tumor recognition. These methods involve screening of large, custom-built, peptide libraries displayed in yeast and mammalian cells to identify surrogate peptides that are recognized by the TCR and drive T cell activation.

Together, the identification of potent peptide agonists and the engineering of novel protein molecules to effectively enhance anti-tumor responses by T cells provide an exciting opportunity to better control the immune response in health and disease and to interrogate fundamental aspects of T cell biology.