0000000000116314
AUTHOR
Hélène Bugaut
Immune ambivalence: The schizophrenic bleomycin.
In addition to cytotoxic effects, anticancer agents can exert multiple immunomodulatory functions. We have recently described the molecular mechanisms whereby bleomycin can 1) promote endoplasmic reticulum stress, causing the immunogenic death of cancer cells and hence strengthening antitumor CD8+ T cell responses; and 2) induce the secretion of transforming growth factor β (TGFβ), which stimulates regulatory T cells. This suggests that bleomycin may be favorably combined with TGFβ-targeting strategies.
SOCS3 transactivation by PPARγ prevents IL-17-driven cancer growth.
Abstract Activation of the transcription factor PPARγ by the n-3 fatty acid docosahexaenoic acid (DHA) is implicated in controlling proinflammatory cytokine secretion, but the intracellular signaling pathways engaged by PPARγ are incompletely characterized. Here, we identify the adapter-encoding gene SOCS3 as a critical transcriptional target of PPARγ. SOCS3 promoter binding and gene transactivation by PPARγ was associated with a repression in differentiation of proinflammatory T-helper (TH)17 cells. Accordingly, TH17 cells induced in vitro displayed increased SOCS3 expression and diminished capacity to produce interleukin (IL)-17 following activation of PPARγ by DHA. Furthermore, naïve CD4…
Bleomycin Exerts Ambivalent Antitumor Immune Effect by Triggering Both Immunogenic Cell Death and Proliferation of Regulatory T Cells
International audience; Bleomycin (BLM) is an anticancer drug currently used for the treatment of testis cancer and Hodgkin lymphoma. This drug triggers cancer cell death via its capacity to generate radical oxygen species (ROS). However, the putative contribution of anticancer immune responses to the efficacy of BLM has not been evaluated. We make here the observation that BLM induces immunogenic cell death. In particular, BLM is able to induce ROS-mediated reticulum stress and autophagy, which result in the surface exposure of chaperones, including calreticulin and ERp57, and liberation of HMBG1 and ATP. BLM induces anti-tumor immunity which relies on calreticulin, CD8(+) T cells and inte…