Suchergebnisse

The search for non-invasive systemic biomarkers of response to PD-L1/PD-1 blockade immunotherapy is currently a priority in oncoimmunology. In contrast to classical tumor biomarkers, the identification of clinically useful immunological biomarkers is certainly a challenge, as anti-cancer immune responses depend on the coordinated action of many cell types. Studies on the dynamics of systemic CD8 T-cell populations have provided indications that such biomarkers may have a place in clinical practice. However, the power of CD8 T-cell subsets to discriminate clinical responses in immunotherapy has so far proven to be limited. The systemic evaluation of CD8 T-cell regulators such as myeloid cells and CD4 T cells may provide the solution. Here we discuss the value of systemic quantification of CD4 T-cell subsets for patient selection in light of the results obtained by Prof. Kagamu′s and our team. Our studies have independently demonstrated that the evaluation of the pre-treatment status of systemic CD4 immunity is a critical factor for the clinical outcome of PD-L1/PD-1 blockade therapy with robust predictive capacities. ; This work was funded by the Spanish Association against Cancer (AECC, PROYE16001ESCO), Instituto de Salud Carlos III (ISCIII, FIS. PI17/02119), Biomedicine Project grant from the Department of Health of the Government of Navarre (BMED 050-2019), JSPS KAKENHI grant number 17H04184, and the Japan Agency for Medical Research and Development (grant nos. 19ae0101074h0001).

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. ; The Oncoimmunology group is funded by the Spanish Association against Cancer (AECC, PROYE16001ESCO); Instituto de Salud Carlos III (ISCIII)-FEDER project grants (FIS PI17/02119, FIS PI20/00010, COV20/00000, and TRANSPOCART ICI19/00069); a Biomedicine Project grant from the Department of Health of the Government of Navarre (BMED 050-2019); Strategic projects from the Department of Industry, Government of Navarre (AGATA, Ref 0011-1411-2020-000013; LINTERNA, Ref. 0011-1411-2020-000033; DESCARTHES, 0011-1411-2019-000058); European Project Horizon 2020 Improved Vaccination for Older Adults (ISOLDA; ID: 848166); Crescendo Biologics Ltd.