Abstract
Abstract Poor infiltration of functioning T cells renders tumors unresponsive to checkpoint-blocking immunotherapies. Here, we employed a combinatorial in situ immunomodulation strategy based on the administration of selected immunogenic drugs and immunotherapy to sensitise two mouse models of neuroblastoma (NB) sparsely infiltrated by T cells to the host antitumor immune response. Using multiple in vitro, ex vivo, and in vivo approaches, we found that mitoxantrone treatment curbed NB growth and promoted tumor regression when combined with TGFβ and PD-1 blockade in aggressive NB models. This combined immunotherapy strategy resulted in the enrichment of a variety of both innate and adaptive immune cells into the TME, and the concomitant production of inflammatory chemokines involved in remodelling the tumor’s immune landscape. Mitoxantrone in combination with TGFβ and PD-1 blockade could be used to reshape the functional repertoire of intratumoral immune cells, restoring the entire immune cell cycle and overcoming the immunosuppressive microenvironment of aggressive NB. Citation Format: Valeria Lucarini, Ombretta Melaiu, Silvia D'Amico, Fabio Pastorino, Patrizia Tempora, Adele De Ninno, Luca Businaro, Mirco Ponzoni, Franco Locatelli, Doriana Fruci. Mitoxantrone in combination with TGFβ and PD-1 blockade remodels the tumor immune landscape enhancing neuroblastoma antitumor immunity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5207.
Published Version
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