Pinto-Fernández Group | Translational Ubiquitomics - Cancer Immunology

Our laboratory investigates how cells fine-tune innate immune signalling to determine whether immune responses protect against disease or contribute to immune evasion and harmful inflammation. We are particularly interested in the ubiquitin and ISG15 systems, and in a class of druggable regulators that we define as Interferon Fine-Tuning Modulators (InFiNeMods). These include deISGylating enzymes and other regulators of type I interferon signalling that control tumour antigenicity, antiviral defence, inflammatory adaptation, and immune resilience.

A major focus of the lab is to understand how cancer cells manipulate interferon signalling to avoid immune recognition and resist therapy. We recently discovered that loss of the deISGylating enzyme USP18, a key negative regulator of the interferon pathway, makes cancer cells more antigenic and more sensitive to radiotherapy. Mechanistically, USP18-deficient cells accumulate innate immune ligands such as double-stranded RNA, enhance antigen-presentation pathways, and activate cytotoxic T cells more efficiently, resulting in increased T-cell killing and improved responses to immunotherapy.

Building on this work, we are now expanding the InFiNeMod framework to additional regulators, including USP16, USP24, and USP5, to understand how distinct molecular nodes shape interferon responses across cancer and infection. Our long-term goal is to develop new therapeutic strategies that restore immune resilience: enhancing protective anti-tumour and antiviral immunity while limiting maladaptive inflammation.

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