Rosa Barreira da Silva

Immunotherapy agents, such as inhibitors of the immune checkpoint Programmed cell death protein 1 (PD-1) or its ligand PD-L1, potentiate cytotoxic CD8 T cell responses against tumor cells and have been approved for the treatment of many cancer types. However, we also recognize that tumors evolve to evade the immune system, motivating us to discover and develop novel ways to achieve sustained anti-tumor immunity.

During my time as a postdoctoral fellow at Genentech, I studied mechanisms that regulate leukocyte migration into tumors with the goal of modulating these pathways in a manner that improves anti-tumor immunity. Specifically, we demonstrated that the key proinflammatory chemokine CXCL10 is altered through post-translational modifications that compromise its function, thus affecting cytotoxic CD8 T cell migration to tumors. Pharmacological inhibition of the extracellular enzyme Dipeptidylpeptidase 4 (DPP4), which truncates CXCL10, restores chemokine function and enhances T cell migration into tumors. My postdoctoral work further elucidated a similar role for DPP4 in limiting eosinophil migration in cancer through the truncation of the chemokine CCL11. Lastly, we described the function the intracellular enzyme Glutaminyl-peptide cyclotransferase-like (QPCTL) in protecting monocyte chemoattractants from inactivation by DPP4. QPCTL inhibition limited monocyte migration into tumors and thereby reshaped the myeloid cell infiltrate to enhance anti-tumor immunity.

My research group in the department of Cancer Immunology investigates mechanisms that impact patient’s responses to cancer immunotherapies, such as checkpoint inhibition, with the goal of discovering new immunoregulatory targets. This reverse translation approach aims to spur research efforts from our plentiful clinical trial data thus enabling next generation immunotherapies.

• Institute Pasteur / Genentech, Postdoctoral fellow in Cancer Immunology – 2012 - 2021
• University of Porto, PhD in Biomedical Sciences and Immunology – 2007 - 2012
• University of Porto, Diploma in Biochemistry – 2002 - 2006

• STAT Wunderkind award – 2020
• Pasteur-Roux Postdoctoral Award – 2013
• The 11th International Symposium on Dendritic Cells Award – 2010
• Riken Research Center for Allergy and Immunology (RCAI) International Summer Program award – 2009
• The 10th International Symposium on Dendritic Cells award – 2008
• Fundação para a Ciência e Tecnologia, Doctoral Award – 2007
• Programa Operacional Ciência e Inovação, Internship Award – 2006