Rodrigo Benedetti Gassen

Inhibition of Tonic PD-1 Signaling in Dendritic Cells Enhances Costimulatory Pathways 2254769

Rodrigo Benedetti Gassen, Karina Lima, Thiago Borges, Christian Garcia et autres

Abstract Introduction Immune checkpoint blockade therapies, particularly those targeting the PD-1/PD-L1 and CTLA-4 pathways, have fundamentally transformed cancer treatment, achieving clinical responses in approximately 25% of patients. Although combinatorial strategies have improved these outcomes, a substantial proportion of patients remain refractory to …

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Oral tributyrin supplementation induces regulatory T cell–mediated immune regulation and prolongs allograft survival in preclinical transplant models

Daniel M. Mendes, João IB Gonçalves, Kaifeng Liu, Heitor P.V. Da Costa et autres

Immunosuppressive drugs remain essential for preventing rejection but carry significant toxicities, underscoring the need for safer, physiology-based immunomodulators. Tributyrin, a prodrug of butyrate with improved systemic bioavailability, has emerged as a metabolically driven immune regulator. Here, we evaluated whether oral tributyrin promotes …

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Immune profiling in a living human recipient of a gene-edited pig kidney

Guilherme Taborda Ribas, André F. Cunha, Jonathan P. Avila, Alessia Giarraputo et autres

Xenotransplantation of gene-edited pig kidneys offers a promising solution to the shortage of kidneys for organ transplantation. We recently performed a gene-edited pig kidney transplantation into a living human recipient with end-stage kidney disease. Here, using transcriptomics, proteomics, metabolomics and multiplexed imaging, …

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A Bead‐Based Screening Platform for Identifying Monoclonal Antibodies That Disrupt PD‐1/PD‐L1 Interactions

Veridiane Maria Pscheidt, Rodrigo Benedetti Gassen, José Tadeu Aranha Nunes, Deise Nascimento de Freitas et autres

Monoclonal antibodies (mAbs) targeting immune checkpoint pathways such as programmed cell death protein 1 (PD‐1)/PD‐L1 are central to modern immunotherapy, yet scalable methods to assess their functional blockade remain limited. We present a bead‐based flow cytometry assay for quantifying the inhibition of …

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Development of a Novel Mouse Model of Focal Segmental Glomerulosclerosis Recurrence Post-Kidney Transplantation Mediated by Anti-Nephrin Antibodies

Mathieu Lafargue, Rodrigo Benedetti Gassen, Yoshikazu Ganchiku, Leonardo Vidal Riella et autres

Purpose: Posttransplant recurrence of primary focal segmental glomerulosclerosis (pFSGS) is a major challenge in kidney transplantation, frequently leading to allograft failure. Autoantibodies against nephrin, a key podocyte protein, have been implicated in disease recurrence, yet their precise pathogenic role remains unclear. Current …

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Mutein IL-2 Attenuates Antigen-Mediated Rejection in Murine Kidney Transplant Model

Yoshikazu Ganchiku, Rodrigo Benedetti Gassen, Zachary H. Shriver, Gregory J. Babcock et autres

Purpose: Antibody-mediated chronic rejection (AMR) remains a major obstacle to long-term graft survival, necessitating the development of more effective therapies. Selective in vivo expansion of regulatory T cells (Tregs) using low-dose IL-2 or its analogs has emerged as a promising strategy for …

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Marchf1 Deficiency Attenuates Antibody-Mediated Rejection by Modulating B Cell Responses

Maofu Liao, Kalil Alves de Lima, Rodrigo Benedetti Gassen, Yoshikazu Ganchiku et autres

Purpose: TNFRSF13B is one of the most polymorphic genes in humans.Low function variants encoded by TNFRSF13B mutant alleles are associated with antibody mediated rejection (AMR) of kidney transplants.This association was confirmed by studies in Tnfrsf13b-deficient mice in which heterotopic cardiac allografts exhibited …

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Marchf1 Ablation in Dendritic Cells Reduces Alloimmunity and Promotes Long-Term Graft Survival

Kelly Goulart Lima, Rodrigo Benedetti Gassen, Yoshikazu Ganchiku, Ming‐Wei Liao et autres

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The inhibitory receptor Siglec-E controls antigen-presenting cell activation and T cell–mediated transplant rejection

Thiago J. Borges, Karina Rodrigues Lima, Rodrigo Benedetti Gassen, Kaifeng Liu et autres

After transplantation, inflammation and tissue injury release danger signals that activate myeloid cells, driving adaptive immune responses and acute rejection. Current immunosuppressants primarily target T cells but inadequately control innate immunity. Regulatory signals controlling innate responses in transplantation remain elusive. The sialic …

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Human type 1 conventional dendritic cells contribute to skin transplant rejection

Thiago J. Borges, Catherine A. A. Lee, Kyla Mucciarone, Karina Rodrigues Lima et autres

cDC1s play an important role in rejecting human skin allografts, and their local modulation is a promising therapeutic approach.

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Exploring immune response toward transplanted human kidney tissues assembled from organoid building blocks

Thiago J. Borges, Yoshikazu Ganchiku, Jeffrey O. Aceves, Ronald C. van Gaal et autres

The increasing scarcity of organs and the significant morbidity linked to dialysis require the development of engineered kidney tissues from human-induced pluripotent stem cells. Integrative approaches that synergize scalable kidney organoid differentiation, tissue biomanufacturing, and comprehensive assessment of their immune response and …

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Notch2+ Marginal zone B cell depletion decreases antigen shuttle to Follicular Dendritic cells and reduces alloantibody production

Rodrigo Benedetti Gassen, Thiago de Jesus Borges, Ciara N. Magee, Naoka Murakami et autres

Abstract Chronic antibody-mediated rejection (CAMR) is a major cause of allograft loss. Most anti-rejection therapies target T cells and novel treatments to suppress CAMR are needed. Notch2+ Marginal zone (MZ) B cells have a key role in rapidly generating antibodies and facilitating …

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