Poly(I:C) primes primary human glioblastoma cells for an immune response invigorated by PD-L1 blockade

Waele, Jorrit De; Marcq, Elly; Audenaerde, Jonas R.M. Van; Loenhout, Jinthe Van; Deben, Christophe; Zwaenepoel, Karen; Kelft, Erik Van de; Planken, David Van der; Menovsky, Tomas; Bergh, Johan Mj Van den; Willemen, Yannick; Pauwels, Patrick; Berneman, Zwi N.; Lardon, Filip; Peeters, Marc; Wouters, An; Smits, Evelien

doi:10.1080/2162402x.2017.1407899

Cited by 37 publications

(49 citation statements)

References 61 publications

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“…5e, f). Since poly(I:C) is a potent inducer of IFN-I [27], we assumed and validated that treatment with poly(I:C) could significantly augment the expression of PD-L1 on LUAD cells in vitro (Fig. 5g).…”

Section: Resultsmentioning

confidence: 88%

Lung adenocarcinoma-intrinsic GBE1 signaling inhibits anti-tumor immunity

Cheng

et al. 2019

Mol Cancer

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Background Changes in glycogen metabolism is an essential feature among the various metabolic adaptations used by cancer cells to adjust to the conditions imposed by the tumor microenvironment. Our previous study showed that glycogen branching enzyme (GBE1) is downstream of the HIF1 pathway in hypoxia-conditioned lung cancer cells. In the present study, we investigated whether GBE1 is involved in the immune regulation of the tumor microenvironment in lung adenocarcinoma (LUAD). Methods We used RNA-sequencing analysis and the multiplex assay to determine changes in GBE1 knockdown cells. The role of GBE1 in LUAD was evaluated both in vitro and in vivo. Results GBE1 knockdown increased the expression of chemokines CCL5 and CXCL10 in A549 cells. CD8 expression correlated positively with CCL5 and CXCL10 expression in LUAD. The supernatants from the GBE1 knockdown cells increased recruitment of CD8 + T lymphocytes. However, the neutralizing antibodies of CCL5 or CXCL10 significantly inhibited cell migration induced by shGBE1 cell supernatants. STING/IFN-I pathway mediated the effect of GBE1 knockdown for CCL5 and CXCL10 upregulation. Moreover, PD-L1 increased significantly in shGBE1 A549 cells compared to those in control cells. Additionally, in LUAD tumor tissues, a negative link between PD-L1 and GBE1 was observed. Lastly, blockade of GBE1 signaling combined with anti-PD-L1 antibody significantly inhibited tumor growth in vivo. Conclusions GBE1 blockade promotes the secretion of CCL5 and CXCL10 to recruit CD8 + T lymphocytes to the tumor microenvironment via the IFN-I/STING signaling pathway, accompanied by upregulation of PD-L1 in LUAD cells, suggesting that GBE1 could be a promising target for achieving tumor regression through cancer immunotherapy in LUAD. Electronic supplementary material The online version of this article (10.1186/s12943-019-1027-x) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 88%

Lung adenocarcinoma-intrinsic GBE1 signaling inhibits anti-tumor immunity

Cheng

et al. 2019

Mol Cancer

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“…(i-k) The correlation analysis of OSMR with IL-6 (i), PD-L1 (j) or LAIR1 (k) in clinical tissues with western blot analysis (PD-L1: r = 0.6077, p = 0.0211; IL-6: r = 0.6107, p = 0.0203; LAIR1: r = 0.6743, p = 0.0115; with Pearson correlation analysis). CGGA: Chinese Glioma Genome Atlas; GBM: glioblastoma; IL: interleukin; OSMR: oncostatin M receptor; RNAseq: RNA sequencing; TCGA: The Cancer Genome Atlas [Color figure can be viewed at wileyonlinelibrary.com] et al De Waele et al, 2018;Lemke et al, 2012;Sharp et al, 2012;Z. Wang et al, 2016;Q.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of oncostatin M receptor regulates local immune response in glioblastoma

Guo

Guan

Cao

et al. 2019

Journal Cellular Physiology

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Glioblastoma (GBM) is the most lethal cancer in central nervous system. It is urgently needed to look for novel therapeutics for GBM. Oncostatin M receptor (OSMR) is a cytokine receptor gene of IL‐6 family and has been reported to be involved in regulating GBM tumorigenesis. However, the role of OSMR regulating the disrupted immune response in GBM need to be further investigated. Three gene expression profiles, Chinese Glioma Genome Atlas (CGGA), The Cancer Genome Atlas (TCGA), and Gene Expression Omnibus (GEO) data set (GSE16011), were enrolled in our study and used for OSMR expression and survival analysis. The expression of OSMR was further verified with immunohistochemistry and western blot analysis in glioma tissues. Microenvironment cell populations‐counter (MCP‐counter) was applied for analyzing the relationship between OSMR expression and nontumor cells. The functions of OSMR in GBM was investigated by Gene Ontology, Gene set enrichment analysis (GSEA), gene set variation analysis and so on. The analysis of cytokine receptor activity‐related genes in glioma identifies OSMR as a gene with an independent predictive factor for progressive malignancy in GBM. Furthermore, OSMR expression is a prognostic marker in the response prediction to radiotherapy and chemotherapy. OSMR contributes to the regulation of local immune response and extracellular matrix process in GBM. Our findings define an important role of OSMR in the regulation of local immune response in GBM, which may suggest OSMR as a possible biomarker in developing new therapeutic immune strategies in GBM.

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“…1, 12,36,193,[206][207][208][209][210][211][212][213] Chemotherapy-driven ICD is typically associated with: (1) surface exposure of calreticulin (CALR), which mediates pro-phagocytic effects, 205,[214][215][216] (2) active or passive release of ATP, which operates as a shortrange 'find me' signal and inflammasome activator; [217][218][219][220][221] (3) passive release of the non-histone chromatin-binding protein high-mobility group box 1 (HMGB1), which operates as an agonist of Toll-like receptor 4 (TLR4) and Advanced glycosylation end-product specific receptor (AGER); 57,222,223 (4) active or passive release of annexin A1 (ANXA1), a formyl peptide receptor 1 (FPR1) agonist; 155 (5) active secretion of immunostimulatory and chemotactic cytokines, including type I interferon (IFN), C-C motif chemokine ligand 2 (CCL2), C-X-C motif chemokine ligand 1 (CXCL1) and CXCL10; 5,24,224-231 and (6) passive release of nucleic acids, which can engage TLR3, TLR7/8 and/or TLR9. [231][232][233] These danger signals have been robustly associated with ICD induced by anthracyclines (i.e. idarubicin, epirubicin, doxorubicin, and mitoxantrone), but some minor, context-dependent variations exist for ICD elicited by cyclophosphamide and bortezomib.…”

Section: Introductionmentioning

confidence: 99%

Trial watch: chemotherapy-induced immunogenic cell death in immuno-oncology

et al. 2020

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The term 'immunogenic cell death' (ICD) denotes an immunologically unique type of regulated cell death that enables, rather than suppresses, T cell-driven immune responses that are specific for antigens derived from the dying cells. The ability of ICD to elicit adaptive immunity heavily relies on the immunogenicity of dying cells, implying that such cells must encode and present antigens not covered by central tolerance (antigenicity), and deliver immunostimulatory molecules such as damage-associated molecular patterns and cytokines (adjuvanticity). Moreover, the host immune system must be equipped to detect the antigenicity and adjuvanticity of dying cells. As cancer (but not normal) cells express several antigens not covered by central tolerance, they can be driven into ICD by some therapeutic agents, including (but not limited to) chemotherapeutics of the anthracycline family, oxaliplatin and bortezomib, as well as radiation therapy. In this Trial Watch, we describe current trends in the preclinical and clinical development of ICD-eliciting chemotherapy as partner for immunotherapy, with a focus on trials assessing efficacy in the context of immunomonitoring.

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Poly(I:C) primes primary human glioblastoma cells for an immune response invigorated by PD-L1 blockade

Cited by 37 publications

References 61 publications

Lung adenocarcinoma-intrinsic GBE1 signaling inhibits anti-tumor immunity

Lung adenocarcinoma-intrinsic GBE1 signaling inhibits anti-tumor immunity

Overexpression of oncostatin M receptor regulates local immune response in glioblastoma

Trial watch: chemotherapy-induced immunogenic cell death in immuno-oncology

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