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Novel Immunotherapy and Clinical Trials - Melero Group

The focus of our research are immunomodulation strategies to make the most of anticancer immune responsesl Our research aims to uncover how second-hand antigen presentation and inflammatory signalling can be harnessed to improve anti-tumour immunity and enhance responses to conventional immunotherapy to immune checkpoint blockade (ICB). We focus on two key immune processes:

Cross-presentation of tumour antigens.

Cross-presentation is a critical process by which specialised antigen-presenting cells, called dendritic cells, capture tumour-derived material and present it to CD8⁺ T cells. This step is essential for initiating and sustaining effective anti-tumour T cell responses, yet it is often inefficient or suppressed within the tumour microenvironment. Our research aims to define the cellular and molecular mechanisms that regulate cross-presentation across different cancer types. By understanding how tumour antigens are processed, presented, and recognised by T cells, we seek to identify strategies that strengthen tumour-specific immunity and improve the effectiveness of ICB therapy. In particular we study the transient cell-to-cell interactions involved termed immune synapses. In this regard, we explore the contribution of costimulation and co inhibitory receptors on the surface of interacting dendritic cells and T cells.

Immuno-inflammatory agents to enhance ICB treatment.

Many tumours fail to respond to immune checkpoint blockade because they exert immunosuppressive activities or display suppressive inflammatory mediators and networks that limit T cell function and antigen presentation. We investigate how  pro-rumor inflammatory agents can reshape the tumour microenvironment to inhibit antigen presentation. Neutralization of these mediators, their receptors or their signaling stimulates anti-cancer innate immune activation, and support durable CD8⁺ T cell-mediated tumour control. Using models and patient-derived samples from multiple cancer types, our work aims to act by means of  using rational combinations of  anti-inflammatory therapies with ICB.  Some of the anti-inflammatory agents can be repurposed from other areas of medicine. We anticipate that these findings will support the development of more effective synergistic treatment strategies for patients who currently do not benefit from checkpoint immunotherapy or other experimental immunotherapy agents.

Our team