Ramiro M. Perrotta

Abstract 2241: Galectin 1 as a regulator of hormone driven mammary remodeling and early dissemination with therapeutic potential in breast cancer.

Magalí Bertón, Ramiro M. Perrotta, Luis Valencia Salazar, Tomas D'alotto Moreno et autres

Abstract Galectin-1 (GAL1) is a glycan-binding protein broadly known to shape tumor progression by promoting immune evasion and metastatic dissemination. While GAL1 is well recognized as an immunomodulator in multiple cancer types, its role in hormone-driven mammary gland biology and early tumor …

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A Developmental Lectin-Glycan Program Enables Early Breast Cancer Dissemination and Metastatic Onset

Ramiro M. Perrotta, Magalí Bertón, Luis Valencia Salazar, Yamil Mahmoud et autres

SUMMARY Early dissemination of breast cancer cells can precede clinically detectable tumor progression, yet the programs enabling this process, remain poorly understood. Here, we identify a developmental glycocheckpoint governed by the galectin-1 (GAL1)-glycan axis that is hijacked during early breast cancer dissemination. …

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Engineered base editors with reduced bystander editing through directed evolution

Ramiro M. Perrotta, Svenja Vinke, Raphaël Ferreira, Michaël Moret et autres

Base editors enable precise genome modification but are constrained by bystander edits that limit their applicability. Existing strategies to enhance precision often compromise efficiency and remain highly sequence dependent. Here we present a parallel engineering approach that optimizes both guide RNAs and …

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Glycosylation-driven programs control the immunosuppressive and pro-tumorigenic activities of small extracellular vesicles 4450

Camila A. Bach, Cecilia E. Verillo, Nicole M. Naranjo, Ramiro M. Perrotta et autres

Abstract Description Breast cancer (BC) and prostate cancer (PCa) metastasis are supported by small extracellular vesicles (EVs) released by regulatory myeloid (mEVs) and tumor (tEVs) cells. Galectin 1 (Gal1) is an endogenous lectin that binds to N- and O-glycans. This binding can …

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Abstract 6165: Antiprogestin- mediated endocrine therapy activates immunotherapy- responsive programs in hormone receptor positive breast tumors

Mariana Salatino, Joaquín P. Merlo, Tomás Dalotto‐Moreno, Magalí Bertón et autres

Abstract The endocrine status of the patient is a critical factor that may modulate the immune response in breast cancer and, accordingly, should be considered during immunotherapy regimens. Given the immunosuppressive and tolerogenic activities of the sexual hormone progesterone and its roles …

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Abstract 107: Galectin-1 plays a critical role in normal and neoplastic mammary gland morphogenesis and metastatic spreading in breast cancer

Magalí Bertón, Ramiro M. Perrotta, Tomás Dalotto‐Moreno, Mahmoud D. Yamil et autres

Abstract Galectins are a family of glycan-binding proteins that regulate neoplastic transformation, angiogenesis, cell adhesion and tumor-immune escape. Galectin-1 (Gal-1), a prototype member of this family, binds to multiple N-acetyllactosamine units in N- and O-glycans on cell surface glycoproteins. Biologically, Gal-1 plays …

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Preventing escape and malfunction of recoded cells due to tRNA base changes

Anush Chiappino-Pepe, Felix Radford, Bogdan Budnik, Hüseyin Taş et autres

Abstract Engineering the genetic code restricts DNA transfer (cellular bioisolation) and enables new chemistries via non-standard amino acid incorporation. These distinct properties make recoded cells state-of-the-art safe technologies. However, evolutionary pressures may endanger the longevity of the recoding. Here, we reveal that …

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Machine Learning and Directed Evolution of Base Editing Enzymes

Ramiro M. Perrotta, Svenja Vinke, Raphaël Ferreira, Michaël Moret et autres

Abstract As we enter the era of CRISPR medicines, base editors (BEs) emerged as one of the most promising tools to treat genetic associated diseases. However, unintended bystander editing beyond the target nucleotide poses a challenge to their translation into effective therapies. …

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1466 Galectin-1 orchestrates a hierarchical tumor to stromal extracellular vesicles system that fosters immune suppression

Camila A. Bach, Ada G. Blidner, Ramiro M. Perrotta, Joaquín P. Merlo et autres

Background Extracellular vesicles (EVs) suppress effector cells and activate immunosuppressive cells in the ‘escape phase’ of tumor immunoediting. Tumor derived EVs contribute to the differentiation and expansion of immunosuppressive cell subsets. Bone marrow-derived cells (BMDCs) can uptake EVs released by 4T1 -a …

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A single-step, rapid, and versatile method for simultaneous detection of cell surface glycan profiles using fluorochrome-conjugated lectins

Nicolás I. Torres, Montana N Manselle Cocco, Ramiro M. Perrotta, Yamil D. Mahmoud et autres

Cell surface glycans play essential roles in diverse physiological and pathological processes and their assessment has important implications in biomedicine and biotechnology. Here we present a rapid, versatile, and single-step multicolor flow cytometry method for evaluation of cell surface glycan signatures using …

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Data from Enhanced Antitumor Immunity via Endocrine Therapy Prevents Mammary Tumor Relapse and Increases Immune Checkpoint Blockade Sensitivity

Gonzalo R. Sequeira, Ana Sahores, Tomás Dalotto‐Moreno, Ramiro M. Perrotta et autres

Abstract 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. …

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Supplementary Data from Enhanced Antitumor Immunity via Endocrine Therapy Prevents Mammary Tumor Relapse and Increases Immune Checkpoint Blockade Sensitivity

Gonzalo R. Sequeira, Ana Sahores, Tomás Dalotto‐Moreno, Ramiro M. Perrotta et autres

Supplementary Materials and methods