Tomas Dalotto-Moreno

Tomas Dalotto-Moreno
National Scientific and Technical Research Council | conicet · IBYME - Instituto de Biología y Medicina Experimental

PhD

About

30
Publications
5,292
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1,278
Citations

Publications

Publications (30)
Article
Full-text available
Hypothyroidism exerts deleterious effects on immunity, but the precise role of the hypothalamic–pituitary–thyroid (HPT) axis in immunoregulatory and tolerogenic programs is barely understood. Here, we investigated the mechanisms underlying hypothyroid‐related immunosuppression by examining the regulatory role of components of the HPT axis. We first...
Article
Full-text available
Sperm acquire the ability to fertilize in a process called capacitation and undergo hyperactivation, a change in the motility pattern, which depends on Ca²⁺ transport by CatSper channels. CatSper is essential for fertilization and it is subjected to a complex regulation that is not fully understood. Here, we report that similar to CatSper, Cdc42 di...
Article
Full-text available
Hypoxia, angiogenesis, and immunosuppression have been proposed to be interrelated events that fuel tumor progression and impair the clinical effectiveness of anti-tumor therapies. Here we present new mechanistic data highlighting the role of hypoxia in fine-tuning CD8 T cell exhaustion in vitro, in an attempt to reconcile seemingly opposite eviden...
Article
Full-text available
The role of active antitumor immunity in hormone receptor–positive (HR+) breast cancer has been historically underlooked. The aim of this study was to determine the contribution of the immune system to antiprogestin-induced tumor growth inhibition using a hormone-dependent breast cancer model. BALB/c-GFP+ bone marrow (BM) cells were transplanted in...
Preprint
Full-text available
Sperm acquire the ability to fertilize in a process called capacitation and undergo hyperactivation, a change in the motility pattern, which depends on Ca ²⁺ transport by CatSper channels. CatSper is essential for fertilization and it is subjected to a complex regulation that is not fully understood. Here, we report that similar to CatSper, Cdc42 d...
Article
Full-text available
The activity and survival of retinal photoreceptors depend on support functions performed by the retinal pigment epithelium (RPE) and on oxygen and nutrients delivered by blood vessels in the underlying choroid. By combining single-cell and bulk RNA sequencing, we categorized mouse RPE/choroid cell types and characterized the tissue-specific transc...
Article
Significance Different immune inhibitory circuits act in concert to prevent and limit the extent of deleterious autoimmune reactions occurring during the aging process. An in-depth understanding of these pathways is critical for implementation of more selective and powerful immunomodulatory modalities capable of attenuating autoimmune inflammation....
Article
Full-text available
Hanahan and Weinberg have proposed 10 organizing principles that enable growth and metastatic dissemination of cancer cells. These distinctive and complementary capabilities, defined as the "hallmarks of cancer," include the ability of tumor cells and their microenvironment to sustain proliferative signaling, evade growth suppressors, resist cell d...
Article
Full-text available
Recent understanding of the mechanisms that control immune system homeostasis and orchestrate antitumor responses has prompted the development of novel immunotherapeutic modalities. These include antibodies that target immune checkpoints such as PD-1/PD-L1 and CTLA-4, agonistic antibodies of costimulatory molecules such as CD137 and OX-40 and the a...
Article
Galectins decode glycan-containing information in a number of cell receptors adjusting signaling thresholds and modulating cellular functions. Upon specific binding to cell surface glycans these lectins control receptor clustering, endocytosis and signaling, influencing many physiological and pathological conditions. In particular, galectin-1 (Gal1...
Article
Full-text available
Mammalian sperm must undergo a functionally defined process called capacitation to be able to fertilize oocytes. They become capacitated in vivo by interacting with the female reproductive tract or in vitro in a defined capacitation medium that contains bovine serum albumin, calcium (Ca²⁺), and bicarbonate (HCO3⁻). In this work, sperm were double s...
Article
Pancreatic ductal adenocarcinoma (PDA) remains one of the most lethal tumor types, with extremely low survival rates due to late diagnosis and resistance to standard therapies. A more comprehensive understanding of the complexity of PDA pathobiology, and especially of the role of the tumor microenvironment in disease progression, should pave the wa...
Article
This abstract was withdrawn by the authors.
Article
The role of the immune system in the regression of mammary carcinomas using endocrine therapies has been poorly investigated. The main goals of this study were: a) to evaluate differences in antiprogestin-induced regression of hormone receptor positive mammary carcinomas growing in immunocompetent or immunodeficient mice; b) to characterize the tum...
Article
The immune system is responsible for recognition and elimination of cancer cells. Tumors, however, can elicit different evasive mechanisms that contribute to immune escape Thus, understanding the immunosuppressive pathways that hamper tumor immunity is critical for the identification of novel therapeutic targets. Progestin-containing hormonal suppl...
Article
The immune system plays key roles in the recognition and elimination of most tumors. Progesterone (Pg) can shape the immune response favoring a tolerogenic rather than a pro-inflammatory adaptive response. As hormone replacement therapies, supplementation and hormone-based contraceptives have been associated with an increase of malignant breast neo...
Article
Full-text available
During the past decade, a better understanding of the cellular and molecular mechanisms underlying tumor immunity has provided the appropriate framework for the development of therapeutic strategies for cancer immunotherapy. Under this complex scenario, galectins have emerged as promising molecular targets for cancer therapy responsible of creating...
Article
Full-text available
Formation of an aberrant and heterogeneous vascular network is a key pathological event in the multistep process of tumor growth and metastasis. Pro-angiogenic factors are synthesized and released from tumor, stromal, endothelial, and myeloid cells in response to hypoxic and immunosuppressive microenvironments which are commonly found during cancer...
Article
The clinical benefit conferred by vascular endothelial growth factors (VEGF)-targeted therapies is variable, and tumors from treated patients eventually reinitiate growth. Here, we identify a glycosylation-dependent pathway that compensates for the absence of cognate ligand and preserves angiogenesis in response to VEGF blockade. Remodeling of the...
Article
Full-text available
The progesterone analog medroxyprogesterone acetate (MPA) is widely used as a hormone replacement therapy in postmenopausal women and as contraceptive. However, prolonged administration of MPA is associated with increased incidence of breast cancer through ill-defined mechanisms. Here, we explored whether exposure to MPA during mammary tumor growth...
Article
Exposure to sexual hormones is one of the strongest risk factors for breast cancer. Increased risk is entwined with a greater number of reproductive cycles and the use of progestin-containing hormone replacement therapy. In addition, the importance of progesterone in dampening immune response was illustrated in several models of infection and pregn...
Article
Full-text available
Novel therapeutic strategies are needed to counteract breast cancer-associated immunosuppression. Silencing the expression of galectin-1 in a breast carcinoma model inhibited tumor growth and prevented lung metastasis by reducing the frequency and immunosuppressive activity of CD4(+)CD25(+) FOXP3(+) regulatory T cells.
Article
Hormone replacement therapy with the progesterone analogue medroxyprogesterone acetate (MPA) is widely used in postmenopausal women for the treatment of endometrial conditions, and as a contraceptive. However, prolonged administration of MPA is associated with increased incidence of breast cancer through ill-defined mechanisms. Our aim was to explo...
Conference Paper
Full-text available
The progesterone analogue medroxyprogesterone acetate (MPA) is being widely used in postmenopausal women, for the treatment of endometrial conditions, and as a contraceptive. However, hormone replacement therapy in postmenopausal women has been associated with increased incidence of breast cancer through ill-defined mechanisms. In this work, we exp...
Article
Full-text available
Galectin-1 (Gal1), an evolutionarily conserved glycan-binding protein, contributes to the creation of an immunosuppressed microenvironment at sites of tumor growth. In spite of considerable progress in elucidating its role in tumor-immune escape, the mechanisms underlying the inhibitory functions of Gal1 remain obscure. Here we investigated the con...
Article
Full-text available
Galectins, a family of endogenous glycan-binding proteins able to recognize specific glycoconjugates on cell surface and extracellular matrix, control critical immunological processes involved in immune homeostasis and tumor progression. Given the immunosuppressive role of Galectin-1 (Gal-1) in different models of chronic inflammation and its contr...

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