GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE266nnn/GSE266346/primaryOK200TranscriptomicsHomo sapiensExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE266346GEOGSEfalseTNF-mediated cell death: an actionable target for immunotherapy in T-ALL [2]T-cell acute lymphoblastic leukemia (T-ALL) accounts for one of the most aggressive hematological tumors and remains associated with poor prognosis and dismal outcomes, notably for relapsed and refractory patients. Unlike leukemias of myeloid or B-cell origin, T-ALL has not benefited from the major advances in immune and cell-based therapies. Hence, an unmet medical need persists for underserved T-ALL patients who fail to durably respond to conventional treatments. Herein, we report the robust antileukemic efficacy of ATG, a polyclonal cocktail of IgG enriched in human thymocyte antigens, in vivo. The treatment of a large series of preclinical models of T-ALL revealed a genuine cytotoxic mechanism of ATG mediated by TNF signaling. Critically, we revealed that ATG resistance may occur via the induction of negative regulators of TNF-induced cell death, and can be circumvented by SMAC mimetic birinapant ex vivo and in vivo. These promising results were validated in an important series of prospective primary R/R T-ALL samples. This study provides a strong rationale for clinically relevant ATG-based immunotherapy in combination with birinapant to better treat T-ALL patients.2026/05/31GSE266346GSM8245409GSM8245408GSM8245438GSM8245416GSM8245415GSM8245437GSM8245418GSM8245439GSM8245417GSM8245412GSM8245434GSM8245433GSM8245411GSM8245436GSM8245414GSM8245435GSM8245413GSM8245430GSM8245432GSM8245410GSM8245431GSM8245419GSM8245427GSM8245405GSM8245426GSM8245429GSM8245407GSM8245406GSM8245428GSM8245423GSM8245422GSM8245425GSM8245424GSM8245441GSM8245440GSM8245421GSM8245442GSM824542018573266346Homo sapiens