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| Item Type: | Preprint |
|---|---|
| Title: | Therapy-induced senescence upregulates antigen presentation machinery and triggers anti-tumor immunity in Acute Myeloid Leukemia |
| Creators Name: | Gilioli, D., Fusco, S., Tavella, T., Giannetti, K., Conti, A., Santoro, A., Carsana, E., Beretta, S., Schönlein, M., Gambacorta, V., Aletti, F.M., Carraba, M.G., Bonini, C., Ciceri, F., Merelli, I., Vago, L., Schmitt, C.A. and Di Micco, R. |
| Abstract: | Acute myeloid leukemia (AML) is an aggressive hematological malignancy often curable only by using intensive chemotherapy. Nonetheless, resistance/early relapses are frequent, underscoring the need to investigate the molecular events occurring shortly after chemotherapy. Therapy-induced senescence (TIS) is a fail-safe tumor suppressive mechanism that may elicit immune-mediated responses contributing to senescent cell clearance. Yet, TIS functional role in AML eradication and immune surveillance early post-chemotherapy remains ill-defined. By combining transcriptional and cellular-based evaluation of senescence markers in AML patient samples, we found upregulation of senescence-associated genes and interferon gene categories with concomitant induction of HLA class I and class II molecules, pointing to a causal link between TIS and leukemia immunogenicity. Consistently, senescence-competent AML samples activated autologous CD4+ and CD8+ T cells and improved leukemia recognition by both T-cell subsets. Lastly, the anti-leukemic activity of Immune Checkpoint Blockades (ICBs) was enhanced upon senescence engagement in AML. Altogether, our results identify senescence as a potent immune-related anti-leukemic mechanism that may rapidly translate into innovative senescence-based strategies to prevent AML relapse. |
| Source: | bioRxiv |
| Publisher: | Cold Spring Harbor Laboratory Press |
| Article Number: | 2022.11.17.515658 |
| Date: | 17 November 2022 |
| Official Publication: | https://doi.org/10.1101/2022.11.17.515658 |
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