CCL22 Signaling in the Tumor Environment

Röhrle, Natascha; Knott, Max; Anz, David

doi:10.1007/978-3-030-36667-4_8

Cited by 40 publications

(32 citation statements)

References 149 publications

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“…We found that there was no difference in CCL17 expression between early- and advanced-stage T/MF SCC samples, while CCL22 expression was significantly decreased in the latter compared to early-stage T/MF SCC samples. Overexpression of CCL22 in human tumors was reportedly associated with increased infiltration of Tregs, along with augmented tumor growth and poor prognosis in breast, gastric, and liver cancer [ 29 – 33 ]. Hirata et al [ 34 ] suggested that CCL22 produced by naïve CD4 + T cells contributed to an increase in Th2 cell numbers in atopic diseases.…”

Section: Discussionmentioning

confidence: 99%

Downregulation of CCL22 and mutated NOTCH1 in tongue and mouth floor squamous cell carcinoma results in decreased Th2 cell recruitment and expression, predicting poor clinical outcome

Liu

Zhou

et al. 2021

BMC Cancer

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Objective Tongue and mouth floor squamous cell carcinoma (T/MF SCC) exhibits a high rate of local recurrence and cervical lymph node metastasis. The effect of the tumor microenvironment on T/MF SCC remains unclear. Materials and methods Transcriptome and somatic mutation data of patients with T/MF SCC were obtained from HNSC projects of the Cancer Genome Atlas. Immune infiltration quantification in early- (clinical stage I–II) and advanced-stage (clinical stage III–IV) T/MF SCC was performed using single sample Gene Set Enrichment Analysis and MCPcounter. Differentially expressed gene data were filtered, and their function was assessed through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. Kaplan–Meier survival curve analysis and Cox regression model were conducted to evaluate the survival of patients with the CCL22 signature. Maftools was used to present the overview of somatic mutations. Results In T/MF SCC, T helper (Th)2 cell counts were significantly increased in patients with early-stage disease compared to those with advanced-stage disease. Expression of the Th2 cell-related chemokine, CCL22, was downregulated in patients with advanced-stage T/MF SCC. Univariate and multivariate Cox analyses revealed that CCL22 was a good prognostic factor in T/MF SCC. A nomogram based on the expression of CCL22 was constructed to serve as a prognostic indicator for T/MF SCC. NOTCH1 mutations were found at a higher rate in patients with advanced-stage T/MF SCC than in those with early-stage T/MF SCC, resulting in the inhibition of the activation of the NOTCH1-Th2 cell differentiation pathway. The expression levels of CCL22, GATA-3, and IL4 were higher in patients with early-stage T/MF SCC than in those with advanced-stage T/MF SCC. Conclusion In T/MF SCC, high expression of CCL22 may promote the recruitment of Th2 cells and help predict a better survival. Mutations in NOTCH1 inhibit the differentiation of Th2 cells, facilitating tumor progression through a decrease in Th2 cell recruitment and differentiation.

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Section: Discussionmentioning

confidence: 99%

Downregulation of CCL22 and mutated NOTCH1 in tongue and mouth floor squamous cell carcinoma results in decreased Th2 cell recruitment and expression, predicting poor clinical outcome

Liu

Zhou

et al. 2021

BMC Cancer

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“…We have demonstrated that LPS/nigericin treatment may induce the secretion of EGF, TGF-a, G-CSF, fractalkine, IL-9, IL-1β, IL-6 and TNFα in both WT and DN Rab5 HCT116 cells. These cytokines may promote formation of inflammatory microenvironments and contribute to the aggressiveness of tumours [ 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 ]. In our study, the secretion of these cytokines was higher in WT Rab5 cells compared to DN Rab5 cells.…”

Section: Discussionmentioning

confidence: 99%

Rab GTPase Mediating Regulation of NALP3 in Colorectal Cancer

et al. 2020

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The NALP3 inflammasome signaling contributes to inflammation within tumor tissues. This inflammation may be promoted by the vesicle trafficking of inflammasome components and cytokines. Rab5, Rab7 and Rab11 regulate vesicle trafficking. However, the role of these proteins in the regulation of inflammasomes remains largely unknown. To elucidate the role of these Rab proteins in inflammasome regulation, HCT-116, a colorectal cancer (CRC) cell line expressing pDsRed-Rab5 wild type (WT), pDsRed-Rab5 dominant-negative (DN), pDsRed-Rab7 WT, pDsRed-Rab7 DN, pDsRed-Rab11 WT and pDsRed-Rab11 DN were treated with lipopolysaccharide (LPS)/nigericin. Inflammasome activation was analyzed by measuring the mRNA expression of NLRP3, Pro-CASP1, RAB39A and Pro-IL-1β, conducting immunofluorescence imaging and western blotting of caspase-1 and analysing the secretion levels of IL-1β using enzyme-linked immunosorbent assay (ELISA). The effects of Rabs on cytokine release were evaluated using MILLIPLEX MAP Human Cytokine/Chemokine Magnetic Bead Panel-Premixed 41 Plex. The findings showed that LPS/nigericin-treated cells expressing Rab5-WT indicated increased NALP3 expression and secretion of the IL-1β as compared to Rab5-DN cells. Caspase-1 was localized in the nucleus and cytosol of Rab5-WT cells but was localized in the cytosol in Rab5-DN cells. There were no any effects of Rab7 and Rab11 expression on the regulation of inflammasomes. Our results suggest that Rab5 may be a potential target for the regulation of NALP3 in the treatment of the CRC inflammation.

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“…Among the most upregulated genes, we saw the ligands Cxcl13, Ccl21a, and Ccl22 and the chemokine receptors Cxcr4 and Ccr7. CCL22 is a homeostatic cytokine that can be produced in response to inflammation and acts through its receptor CCR4 to control immune activation in the lymph node [29,30]. The CCL21/CCR7 axis has a dual role, since it can both regulate the homing of immune cells to the lymph node to prime and activate T cells, B cells, and dendritic cells [31] and be involved in a metastatic tumor phenotype by promoting cancer cells migration [32,33].…”

Section: Discussionmentioning

confidence: 99%

Inhibition of WHSC1 Allows for Reprogramming of the Immune Compartment in Prostate Cancer

Want

Karasik

Gillard

et al. 2021

IJMS

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Immunotherapy initially demonstrated promising results in prostate cancer (PCa), but the modest or negative results of many recent trials highlight the need to overcome the poor immunogenicity of this cancer. The design of effective therapies for PCa is challenged by the limited understanding of the interface between PCa cells and the immune system in mediating therapeutic resistance. Prompted by our recent observations that elevated WHSC1, a histone methyltransferase known to promote progression of numerous cancers, can silence antigen processing and presentation in PCa, we performed a single-cell analysis of the intratumoral immune dynamics following in vivo pharmacological inhibition of WHSC1 in mice grafted with TRAMP C2 cells. We observed an increase in cytotoxic T and NK cells accumulation and effector function, accompanied by a parallel remodeling of the myeloid compartment, as well as abundant shifts in key ligand–receptor signaling pathways highlighting changes in cell-to-cell communication driven by WHSC1 inhibition. This comprehensive profiling of both immune and molecular changes during the course of WHSC1 blockade deepens our fundamental understanding of how anti-tumor immune responses develop and can be enhanced therapeutically for PCa.

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CCL22 Signaling in the Tumor Environment

Cited by 40 publications

References 149 publications

Downregulation of CCL22 and mutated NOTCH1 in tongue and mouth floor squamous cell carcinoma results in decreased Th2 cell recruitment and expression, predicting poor clinical outcome

Downregulation of CCL22 and mutated NOTCH1 in tongue and mouth floor squamous cell carcinoma results in decreased Th2 cell recruitment and expression, predicting poor clinical outcome

Rab GTPase Mediating Regulation of NALP3 in Colorectal Cancer

Inhibition of WHSC1 Allows for Reprogramming of the Immune Compartment in Prostate Cancer

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