Activation of NF-κB and p300/CBP potentiates cancer chemoimmunotherapy through induction of MHC-I antigen presentation.
Yixuan Zhou,Ingmar N. Bastian,Mark D. Long,Michelle Dow,Wei-Hua Li,Tao Liu,Rachael Katie Ngu,Laura Antonucci,Jian Yu Huang,Qui T. Phung,Xi-he Zhao,Xi-he Zhao,Sourav Banerjee,Sourav Banerjee,Xue-Jia Lin,Xue-Jia Lin,Hongxia Wang,Brian Dang,Sylvia Choi,Daniel Karin,Hua Su,Mark H. Ellisman,Christina Jamieson,Marcus Bosenberg,Zhang Cheng,Johannes Haybaeck,Johannes Haybaeck,Lukas Kenner,Lukas Kenner,Kathleen M. Fisch,Richard Bourgon,Genevive Hernandez,Jennie R. Lill,Song Liu,Hannah Carter,Ira Mellman,Michael Karin,Shabnam Shalapour,Shabnam Shalapour +38 more
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TLDR
In this article, the lysine acetyl transferases p300/CREB binding protein (CBP) and p300 ablations prevent chemotherapy-induced MHC-I AgPPM expression and neoantigen amounts in human cancers.Abstract:
Many cancers evade immune rejection by suppressing major histocompatibility class I (MHC-I) antigen processing and presentation (AgPP). Such cancers do not respond to immune checkpoint inhibitor therapies (ICIT) such as PD-1/PD-L1 [PD-(L)1] blockade. Certain chemotherapeutic drugs augment tumor control by PD-(L)1 inhibitors through potentiation of T-cell priming but whether and how chemotherapy enhances MHC-I-dependent cancer cell recognition by cytotoxic T cells (CTLs) is not entirely clear. We now show that the lysine acetyl transferases p300/CREB binding protein (CBP) control MHC-I AgPPM expression and neoantigen amounts in human cancers. Moreover, we found that two distinct DNA damaging drugs, the platinoid oxaliplatin and the topoisomerase inhibitor mitoxantrone, strongly up-regulate MHC-I AgPP in a manner dependent on activation of nuclear factor kappa B (NF-κB), p300/CBP, and other transcription factors, but independently of autocrine IFNγ signaling. Accordingly, NF-κB and p300 ablations prevent chemotherapy-induced MHC-I AgPP and abrogate rejection of low MHC-I-expressing tumors by reinvigorated CD8+ CTLs. Drugs like oxaliplatin and mitoxantrone may be used to overcome resistance to PD-(L)1 inhibitors in tumors that had "epigenetically down-regulated," but had not permanently lost MHC-I AgPP activity.read more
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Immunogenic cell stress and death
TL;DR: Kroemer et al. as mentioned in this paper found that normal cells succumbing to conditions that promote the formation of post-translational neoantigens (for example, oxidative stress) can also drive at least some degree of antigen-specific immunity, pointing to a novel implication of ICD in the etiology of non-infectious, non-malignant disorders linked to autoreactivity.
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Regulation of antitumor immunity by inflammation-induced epigenetic alterations.
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The immune modifying effects of chemotherapy and advances in chemo-immunotherapy
TL;DR: In this paper , past and present attempts to advance chemo-immunotherapy in difficult-to-treat cancer histologies, mechanisms through which select chemotherapies modify tumor immunogenicity, as well as important considerations when designing such approaches to maximize efficacy and improve therapeutic response rates.
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Syrbactin-class dual constitutive- and immuno-proteasome inhibitor TIR-199 impedes myeloma-mediated bone degeneration <i>in vivo</i>
TL;DR: TIR-199 as discussed by the authors is a syrbactin-class proteasome inhibitor derived from a plant virulence factor of bacterium Pseudomonas syringae pv syringa.
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ATAC-seq: A Method for Assaying Chromatin Accessibility Genome-Wide
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