May 18, 2023
Interruption of the intratumor CD8:Treg crosstalk improves the efficacy of PD-1 immunotherapy
Geels S, Moshensky A, Sousa R, Walker B, Singh R, Gutierrez G, Hwang M, Mempel T, Nie Q, Othy S, and Marangoni F
BioRxiv 2023.05.15.540889; doi: https://doi.org/10.1101/2023.05.15.540889
We elucidate the mechanisms by which PD-1 immunotherapy boosts tumor Tregs in immunogenic tumors. We find no role for Treg-intrinsic blockade of PD-1. Conversely, PD-1 enhnces a CD8 / IL-2 / ICOS / Treg communication axis that prolongs Treg survival. Sequential blockade of ICOS and PD-1 signaling improves the therapeutic efficacy of PD-1 immunotherapy against melanoma.
June 21, 2021
Expansion of tumor-associated Treg cells upon disruption of a CTLA-4-dependent feedback loop
Marangoni F, Zhakyp A, Corsini M, Geels S, Carrizosa E, Thelen M, Mani V, Prüßmann J, Warner R, Ozga A, Di Pilato M, Othy S and Mempel T
Cell 2021, 184(15):3998-4015.e19.
Here we define the mechanisms of intratumor activation of Treg cells using intravital microscopy. We discover that Treg cells self-regulate their own population size through CTLA-4. Its inhibition leads to Treg cell expansion and prevents full therapeutic efficacy against tumors.
March 20, 2019
Guidance Factors Orchestrating Regulatory T Cell Positioning in Tissues during Development, Homeostasis, and Response
Mempel T and Marangoni F
Immunological Reviews 2019, 289(1):129-41
This review manuscript was commissioned in consideration of our work describing the signals Treg receive in distinct tissues, which concur to shape immunological tolerance to cancer.
May 15, 2018
Tumor Tolerance-Promoting Function of Regulatory T Cells is Optimized by CD28, but Strictly Dependent on Calcineurin
Marangoni F, Zhang R, Mani V, Thelen M, Ali Akbar N, Warner R, Äijö T, Zappulli V, Martinez G, Turka L, Mempel T
Journal of Immunology 2018, 200(10):3647-61
This paper establishes the signaling requirements for T regulatory cells in order to establish immunological tolerance to cancer.
February 21, 2013
The Transcription Factor NFAT Exhibits Signal Memory during Serial T Cell Interactions with Antigen Presenting Cells
Marangoni F, Murooka T, Manzo T, Kim E, Carrizosa E, Elpek N, Mempel T
Immunity 2013, 38(2):237-49
This is the first report of signaling dynamics analyzed by intravital microscopy. I demonstrate that slow NFAT deactivation kinetics upon disengagement of T cells from APC contribute to T cell exhaustion.
June 1, 2009
Evidence for long term efficacy and safety of gene therapy for Wiskott-Aldrich Syndrome in preclinical models
Marangoni F, Bosticardo M, Charrier S, Draghici E, Locci M, Scaramuzza S, Panaroni C, Ponzoni M, Sanvito F, Doglioni C, Liabeuf M, Gjata B, Montus M, Siminovitch K, Aiuti A, Naldini L, Dupré L, Roncarolo M, Galy A, Villa A
Molecular Therapy 2009, 17(6):1073-82
This work demonstrates the correction of WAS in preclinical models without side effects using a WASP-encoding lentiviral vector, and was instrumental to obtain the Orphan Drug designation for it.
February 19, 2007
WASP Regulates Suppressor Activity of Human and Murine CD4+CD25+FOXP3+ Natural Regulatory T Cells
Marangoni F, Trifari S, Scaramuzza S, Panaroni C, Martino S, Notarangelo L, Baz Z, Metin A, Cattaneo F, Villa A, Aiuti A, Battaglia M, Roncarolo M, Dupré L
Journal of Experimental Medicine 2007, 204(2):369-80
This work demonstrates the dysfunction of T regulatory cell in Wiskott-Aldrich Syndrome, and proposes it to be the cause of autoimmunity in affected individuals.
March 1, 2006
Efficacy of a gene therapy protocol for Wiskott-Aldrich syndrome based on a WAS promoter/cDNA containing lentiviral vector and non-lethal irradiation
Dupré L *, Marangoni F *, Scaramuzza S, Trifari S, Jofra-Hernandez R, Aiuti A, Naldini L, Roncarolo M
(* contributed equally)
Human Gene Therapy 2006, 17(3):303-13
This paper gives the in vivo proof of principle that lentiviruses containing the WASP promoter are superior tools for WAS gene therapy.