Peer-reviewedCC BY-NC-NDNature communications
Anti-thymocyte globulin triggers TNF-dependent cell death in T-cell acute lymphoblastic leukemia.
12 affiliations
- 1Université de Paris Cité, Institut Necker-Enfants Malades (INEM), Institut national de la santé et de la recherche médicale (Inserm) U1151, and Laboratory of Onco-Hematology, Assistance Publique-Hôpitaux de Paris, Hôpital Necker Enfants-Malades, Paris, France.
- 2Université de Paris Cité, Department of Pediatric Hematology and Immunology, Robert Debré University Hospital (AP-HP), Paris, France.
- 3AP-HP, Hôpital Saint Louis, Unité d'Hématologie, Paris, France.
- 4Department of Pediatric Hematology and Oncology, Assistance Publique-Hôpitaux de Paris (AP-HP), GH HUEP, Armand Trousseau Hospital, Paris, France and Sorbonne Universités, UPMC Univ Paris 06, UMRS 938, CDR Saint-Antoine, GRC n°07, GRC MyPAC, Paris, France.
- 5PRES LUNAM, CHU Angers service des Maladies du Sang et CRCINA INSERM, Angers, France.
- 6Université de Paris, Institut de Recherche Saint-Louis, Paris, France.
- 7INSERM, U1163, Institut Imagine, Paris, France.
- 8AP-HP, Hôpital Saint Louis, Unité d'Hématologie Adolescents et Jeunes Adultes, Paris, France.
- 9Institut Curie, UMR3348, Orsay, France, CNRS UMR3348, Centre Universitaire, Orsay, University Paris-Saclay, Orsay, France.
- 10Service d'Hématologie - Centre Hospitalier de Versailles et U1184, CEA, Université Versailles Paris Saclay, Le Chesnay, France.
- 11Université de Paris Cité, Institut Necker-Enfants Malades (INEM), Institut national de la santé et de la recherche médicale (Inserm) U1151, and Laboratory of Onco-Hematology, Assistance Publique-Hôpitaux de Paris, Hôpital Necker Enfants-Malades, Paris, France. [email protected].
- 12Université de Paris Cité, Institut Necker-Enfants Malades (INEM), Institut national de la santé et de la recherche médicale (Inserm) U1151, and Laboratory of Onco-Hematology, Assistance Publique-Hôpitaux de Paris, Hôpital Necker Enfants-Malades, Paris, France. [email protected].
Abstract
T-cell acute lymphoblastic leukemia (T-ALL) accounts for one of the most aggressive hematological tumors associated with poor prognosis, notably for relapsed and refractory patients. Hence, an unmet medical need persists for T-ALL patients who fail to durably respond to conventional treatments. Herein, we report the antileukemic efficacy of anti-thymocyte globulin (ATG), a polyclonal cocktail of IgG enriched in antibodies directed against human thymocyte antigens. The treatment of preclinical models of T-ALL reveals a cytotoxic mechanism of ATG mediated by TNFα signaling. We demonstrate that ATG resistance may occur via the induction of negative regulators of TNFα-induced cell death and can be circumvented by SMAC mimetic birinapant ex vivo and in vivo. These results are validated in a series of prospective primary relapsed/refractory T-ALL samples. Here, we provide a strong rationale for clinically relevant ATG-based immunotherapy in combination with birinapant to treat T-ALL patients.
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BibTeX
@article{dourthe2026antithymocyte,
title = {{Anti-thymocyte globulin triggers TNF-dependent cell death in T-cell acute lymphoblastic leukemia.}},
author = {Marie Emilie Dourthe and Mehdi Latiri and Etienne Lengliné and Guillaume Charbonnier and Chaimae Saji and Grégoire Huré and Camille Gillet and Jérôme Doss and Aurore Touzart and Lucien Courtois and Agata Cieslak and Mathieu Simonin and Norbert Ifrah and Hervé Dombret and Olivier Hermine and Nicolas Boissel and André Baruchel and Jacques Ghysdael and Elizabeth Macintyre and Philippe Rousselot and Christine Tran Quang and Guillaume P Andrieu and Vahid Asnafi},
journal = {Nature communications},
year = {2026},
month = sep,
doi = {10.1038/s41467-026-77027-9},
url = {https://europepmc.org/article/MED/42901909},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Anti-thymocyte globulin triggers TNF-dependent cell death in T-cell acute lymphoblastic leukemia.
AU - Marie Emilie Dourthe
AU - Mehdi Latiri
AU - Etienne Lengliné
AU - Guillaume Charbonnier
AU - Chaimae Saji
AU - Grégoire Huré
AU - Camille Gillet
AU - Jérôme Doss
AU - Aurore Touzart
AU - Lucien Courtois
AU - Agata Cieslak
AU - Mathieu Simonin
AU - Norbert Ifrah
AU - Hervé Dombret
AU - Olivier Hermine
AU - Nicolas Boissel
AU - André Baruchel
AU - Jacques Ghysdael
AU - Elizabeth Macintyre
AU - Philippe Rousselot
AU - Christine Tran Quang
AU - Guillaume P Andrieu
AU - Vahid Asnafi
PY - 2026
DA - 2026/09/19
JO - Nature communications
DO - 10.1038/s41467-026-77027-9
UR - https://europepmc.org/article/MED/42901909
AB - T-cell acute lymphoblastic leukemia (T-ALL) accounts for one of the most aggressive hematological tumors associated with poor prognosis, notably for relapsed and refractory patients. Hence, an unmet medical need persists for T-ALL patients who fail to durably respond to conventional treatments. Herein, we report the antileukemic efficacy of anti-thymocyte globulin (ATG), a polyclonal cocktail of IgG enriched in antibodies directed against human thymocyte antigens. The treatment of preclinical models of T-ALL reveals a cytotoxic mechanism of ATG mediated by TNFα signaling. We demonstrate that ATG resistance may occur via the induction of negative regulators of TNFα-induced cell death and can be circumvented by SMAC mimetic birinapant ex vivo and in vivo. These results are validated in a series of prospective primary relapsed/refractory T-ALL samples. Here, we provide a strong rationale for clinically relevant ATG-based immunotherapy in combination with birinapant to treat T-ALL patients.
SN - 2041-1723
ER -