GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE266nnn/GSE266344/primaryOK200TranscriptomicsHomo sapiensExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE266344GEOGSEfalseTNF-mediated cell death: an actionable target for immunotherapy in T-ALL [1]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.2026/05/31GSE266344GSM8245380GSM8245379GSM8245378GSM8245375GSM8245374GSM8245377GSM8245376GSM8245382GSM8245381GSM8245384GSM8245373GSM824538324676266344Homo sapiens