Triple-modality therapy maximizes antitumor immune responses in a mouse model of mesothelioma

• DOI: 10.1126/scitranslmed.abd9882
• Publication Date: 2021-04-14T20:51:41Z
• Authors: Junichi Murakami; Licun Wu; Mikihiro Kohno; Mei-Lin Chan; Yidan Zhao; Zhihong Yun; B. C. John Cho; Marc de Perrot
• Keywords: Modality (human–computer interaction); Treatment modality

Malignant pleural mesothelioma (MPM) is an intractable disease with extremely poor prognosis. Our clinical protocol for MPM of subablative radiotherapy (RT) followed by radical surgery achieved better survival compared to other multimodal treatments, but local relapse and metastasis remain a problem. This RT elicits antitumoral immune response that limited the immunosuppressive microenvironment generated regulatory T (Treg) cells. The antitumor effect immunotherapy simultaneously modulate activation suppression after has not been investigated in MPM. Herein, we demonstrated rationale combine interleukin-15 (IL-15) superagonist (IL-15SA) glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR) agonist (DTA-1) mesothelioma. IL-15SA boosted systemic expansion specific memory CD8+ cells were induced mice. Their effect, however, was up-regulation Treg radiated microenvironment. Hence, selective depletion intratumoral through DTA-1 enhanced benefit combination IL-15SA. addition surgical resection maximized accompanied reproducible abscopal concomitant model. These data support development trials test such treatment options patients locally advanced or metastatic tumors.