16 documents found, page 1 of 2
Dissection of the microRNA transcriptomes of CD4+ T cell subsets in autoimmune ...
Cunha, Carolina; Romero, Paula Vargas; Inácio, Daniel; Pais, Ana Teresa; Pelicano, Catarina; Costa, Marina; Mensurado, Sofia; Gonçalves-Sousa, NatachaMicroRNAs (miRNAs) are key regulators of CD4+ T cell differentiation, but how they contribute to the course of an autoimmune disease in vivo remains poorly studied. Given the known roles in autoimmunity of pro-inflammatory T helper 1 (Th)1 and Th17 cells, and anti-inflammatory Foxp3+ regulatory cells, we established a triple reporter mouse for Ifng, Il17 and Foxp3, and subjected it to experimental autoimmune en...
Dual modulation of cytotoxic and checkpoint receptors tunes the efficacy of ado...
Blanco Dominguez, Rafael; Barros, Leandro; Carreira, Mariana; van der Ploeg, Manon; Condeço, Carolina; Marsères, Gabriel; Ferreira, CristinaColorectal cancer (CRC) remains a challenge for current immunotherapies. Vδ1+ γδ T cells offer a promising alternative because of their HLA-I-independent cytotoxicity and natural tissue tropism. We developed Delta One T (DOT) cells, a Vδ1+ γδ T cell-based adoptive cell therapy clinically explored for hematological malignancies but not yet for solid tumors. Here we demonstrate the capacity of DOT cells to target...
Sustained macrophage reprogramming is required for CD8+ T cell–dependent long-t...
Jardim, Carolina; Bica, Marta; Reis-Sobreiro, Mariana; Mota, Afonso Teixeira da; Lopes, Raquel; Ferreira-Pinto, Miguel Alexandre; Sousa, Neuza S.Tumor-associated macrophages (TAM) exhibit a dual role in tumor progression and antitumor immunity. However, understanding the functional states and molecular mechanisms of antitumor TAMs remains a challenge. Herein, we show that intratumoral administration of a combination of agonists against TLR3 and CD40 [hereafter termed myeloid cell treatment (MCT)] reprogrammed TAMs in situ to adopt a protective antitumor...
CD155/PVR determines acute myeloid leukemia targeting by Delta One T cells
Mensurado, Sofia; Condeço, Carolina; Sánchez-Martínez, Diego; Shirley, Sara; Coelho, Rui; Tirado, Néstor; Vinyoles, Meritxell; Blanco Dominguez, RafaelRelapsed or refractory acute myeloid leukemia (AML) remains a major therapeutic challenge. We have recently developed a Vδ1+ γδ T cell-based product for adoptive immunotherapy, named Delta One T (DOT) cells, and demonstrated their cytolytic capacity to eliminate AML cell lines and primary blasts in vitro and in vivo. However, the molecular mechanisms responsible for the broad DOT-cell recognition of AML cells r...
Dissecting the role of microRNAs in effector versus regulatory CD4+ T cell diff...
Cunha, Carolina; Romero, Paula Vargas; Inácio, Daniel; Pais, Ana Teresa; Pelicano, Catarina; Sobral, Daniel; Costa, Marina; Mensurado, SofiaIntroduction: MicroRNAs (miRNAs) are small non-coding RNAs that negatively regulate gene expression at the post-transcriptional level. They have been implicated in the regulation of the differentiation and function of CD4+ T cell subsets, key players in host defense against pathogens, but also responsible for immune-mediated diseases depending on the correct vs incorrect balance, respectively, between pro-infla...
Maternal γδ T cells shape offspring pulmonary type 2 immunity in a microbiota-d...
Papotto, Pedro H.; Yilmaz, Bahtiyar; Pimenta, Gonçalo; Mensurado, Sofia; Cunha, Carolina; Fiala, Gina; Gomes Da Costa, Daniel; Gonçalves-Sousa, NatachaImmune development is profoundly influenced by vertically transferred cues. However, little is known about how maternal innate-like lymphocytes regulate offspring immunity. Here, we show that mice born from γδ T cell-deficient (TCRδ-/-) dams display an increase in first-breath-induced inflammation, with a pulmonary milieu selectively enriched in type 2 cytokines and type 2-polarized immune cells, when compared ...
γδ T cells maintain sensitivity to immunotherapy in MHC-I-deficient tumors
Silva-Santos, Bruno; Mensurado, SofiaLoss of human leukocyte antigen (HLA) class I expression is a major immune evasion mechanism, given the strict requirement of HLA-class-I-mediated antigen presentation for cytotoxic CD8+ T cell activation and tumor cell recognition. In that context, how tumors may remain sensitive to immunotherapy, namely immune checkpoint blockade (ICB), is a highly relevant biological and medical question. A recent study in N...
Therapeutic avenues for γδ T cells in cancer
Costa, Gonçalo Palrão; Mensurado, Sofia; Silva-Santos, Brunoγδ T cells are regarded as promising effector lymphocytes for next-generation cancer immunotherapies. In spite of being relatively rare in human peripheral blood, γδ T cells are more abundant in epithelial tissues where many tumors develop, and have been shown to actively participate in anticancer immunity as cytotoxic cells or as "type 1" immune orchestrators. A major asset of γδ T cells for tackling advanced ...
Generation and proof-of-concept for allogeneic CD123 CAR-Delta One T (DOT) cell...
Sánchez Martínez, Diego; Tirado, Néstor; Mensurado, Sofia; Martínez-Moreno, Alba; Romecín, Paola; Gutiérrez Agüera, Francisco; Correia, Daniel V.Background: Chimeric antigen receptor (CAR)-T cells have emerged as a breakthrough treatment for relapse/refractory hematological tumors, showing impressive complete remission rates. However, around 50% of the patients relapse before 1-year post-treatment. T-cell 'fitness' is critical to prolong CAR-T persistence and activity. Allogeneic T cells from healthy donors are less dysfunctional or exhausted than autol...
Battle of the γδ T cell subsets in the gut
Mensurado, Sofia; Silva-Santos, BrunoIn a study in Science, Reis et al. describe a temporal segregation of γδ T cell activities in colorectal cancer (CRC). Initially tumor surveillance is orchestrated by interferon-γ (IFN-γ)-producing and cytotoxic γδ T cell subsets, but once the tumor thrives, it becomes infiltrated by interleukin (IL)-17+ γδ T cell subsets that promote its growth.