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Chocarro de Erauso, Luisa

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https://academica-e.unavarra.es/handle/2454/48849

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Chocarro de Erauso

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Luisa

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Ciencias de la Salud

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0000-0001-7384-9847

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TA108719

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2021 - 20223
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Subject: Immune checkpoint ×

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Now showing 1 - 3 of 3
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    PublicationOpen Access
    Systemic CD4 immunity and PD-L1/PD-1 blockade immunotherapy
    (MDPI, 2022) Escors Murugarren, David; Bocanegra Gondán, Ana Isabel; Chocarro de Erauso, Luisa; Blanco, Ester; Piñeiro Hermida, Sergio; Garnica, Maider; Fernández Rubio, Leticia; Vera García, Ruth; Arasanz Esteban, Hugo; Kochan, Grazyna; Ciencias de la Salud; Osasun Zientziak
    PD-L1/PD-1 blockade immunotherapy has changed the therapeutic approaches for the treatment of many cancers. Nevertheless, the mechanisms underlying its efficacy or treatment failure are still unclear. Proficient systemic immunity seems to be a prerequisite for efficacy, as recently shown in patients and in mouse models. It is widely accepted that expansion of anti-tumor CD8 T cell populations is principally responsible for anti-tumor responses. In contrast, the role of CD4 T cells has been less studied. Here we review and discuss the evidence supporting the contribution of CD4 T cells to anti-tumor immunity, especially recent advances linking CD4 T cell subsets to efficacious PD-L1/PD-1 blockade immunotherapy. We also discuss the role of CD4 T cell memory subsets present in peripheral blood before the start of immunotherapies, and their utility as predictors of response.
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    PublicationOpen Access
    Understanding LAG-3 Signaling
    (MDPI, 2021) Chocarro de Erauso, Luisa; Blanco, Ester; Zuazo Ibarra, Miren; Arasanz Esteban, Hugo; Bocanegra Gondán, Ana Isabel; Fernández Rubio, Leticia; Morente Sancho, Pilar; Fernández Hinojal, Gonzalo; Echaide Górriz, Míriam; Garnica, Maider; Ramos, Pablo; Vera García, Ruth; Kochan, Grazyna; Escors Murugarren, David; Ciencias de la Salud; Osasun Zientziak; Gobierno de Navarra / Nafarroako Gobernua
    Lymphocyte activation gene 3 (LAG-3) is a cell surface inhibitory receptor with multiple biological activities over T cell activation and effector functions. LAG-3 plays a regulatory role in immunity and emerged some time ago as an inhibitory immune checkpoint molecule comparable to PD-1 and CTLA-4 and a potential target for enhancing anti-cancer immune responses. LAG-3 is the third inhibitory receptor to be exploited in human anti-cancer immunotherapies, and it is considered a potential next-generation cancer immunotherapy target in human therapy, right next to PD-1 and CTLA-4. Unlike PD-1 and CTLA-4, the exact mechanisms of action of LAG-3 and its relationship with other immune checkpoint molecules remain poorly understood. This is partly caused by the presence of non-conventional signaling motifs in its intracellular domain that are different from other conventional immunoregulatory signaling motifs but with similar inhibitory activities. Here we summarize the current understanding of LAG-3 signaling and its role in LAG-3 functions, from its mechanisms of action to clinical applications.
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    PublicationOpen Access
    Clinical landscape of LAG-3-targeted therapy
    (Elsevier, 2022) Chocarro de Erauso, Luisa; Blanco, Ester; Arasanz Esteban, Hugo; Fernández Rubio, Leticia; Bocanegra Gondán, Ana Isabel; Echaide Górriz, Míriam; Garnica, Maider; Ramos, Pablo; Fernández Hinojal, Gonzalo; Vera García, Ruth; Kochan, Grazyna; Escors Murugarren, David; Ciencias de la Salud; Osasun Zientziak; Gobierno de Navarra / Nafarroako Gobernua
    Lymphocyte-activated gene 3 (LAG-3) is a cell surface inhibitory receptor and a key regulator of immune homeostasis with multiple biological activities related to T-cell functions. LAG-3 is considered a next-generation immune checkpoint of clinical importance, right next to programmed cell death protein 1 (PD-1) and cytotoxic T-cell lymphocyte antigen-4 (CTLA-4). Indeed, it is the third inhibitory receptor to be exploited in human anticancer immunotherapies. Several LAG-3-antagonistic immunotherapies are being evaluated at various stages of preclinical and clinical development. In addition, combination therapies blocking LAG-3 together with other immune checkpoints are also being evaluated at preclinical and clinical levels. Indeed, the co-blockade of LAG-3 with PD-1 is demonstrating encouraging results. A new generation of bispecific PD-1/LAG-3-blocking agents have also shown strong capacities to specifically target PD-1+ LAG-3+ highly dysfunctional T cells and enhance their proliferation and effector activities. Here we identify and classify preclinical and clinical trials conducted involving LAG-3 as a target through an extensive bibliographic research. The current understanding of LAG-3 clinical applications is summarized, and most of the publically available data up to date regarding LAG-3-targeted therapy preclinical and clinical research and development are reviewed and discussed.