Granzyme B production by activated B cells derived from breast cancer-draining lymph nodes

Arabpour, Mohsen; Rasolmali, Reza; Talei, Abdolrasoul; Mehdipour, Fereshteh; Ghaderi, Abbas

doi:10.1016/j.molimm.2019.07.019

Cited by 23 publications

(16 citation statements)

References 21 publications

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“…The autophagy targeting cancer cells promotes tumor regression by promoting the elimination of NK cells (Viry et al, 2014). Subpopulations of naive and memory B cells also express GZMB in mammary gland draining lymph nodes (Arabpour et al, 2019). Oncogenic signaling of Kit tyrosine kinase selectively occurs in the Golgi apparatus in the gastrointestinal stromal tumors and causing inhibition of the carcinogenesis by blocking the secretory transport of M-COPA in the gastrointestinal stromal tumors (Obata et al, 2018;Obata et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

Identification of 10 Hub genes related to the progression of colorectal cancer by co-expression analysis

Meng

Liao

et al. 2020

PeerJ

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Background Colorectal cancer (CRC) is the third most common cancer in the world. The present study is aimed at identifying hub genes associated with the progression of CRC. Method The data of the patients with CRC were obtained from the Gene Expression Omnibus (GEO) database and assessed by weighted gene co-expression network analysis (WGCNA), Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses performed in R by WGCNA, several hub genes that regulate the mechanism of tumorigenesis in CRC were identified. Differentially expressed genes in the data sets GSE28000 and GSE42284 were used to construct a co-expression network for WGCNA. The yellow, black and blue modules associated with CRC level were filtered. Combining the co-expression network and the PPI network, 15 candidate hub genes were screened. Results After validation using the TCGA-COAD dataset, a total of 10 hub genes (MT1X, MT1G, MT2A, CXCL8, IL1B, CXCL5, CXCL11, IL10RA, GZMB, KIT) closely related to the progression of CRC were identified. The expressions of MT1G, CXCL8, IL1B, CXCL5, CXCL11 and GZMB in CRC tissues were higher than normal tissues (p-value < 0.05). The expressions of MT1X, MT2A, IL10RA and KIT in CRC tissues were lower than normal tissues (p-value < 0.05). Conclusions By combinating with a series of methods including GO enrichment analysis, KEGG pathway analysis, PPI network analysis and gene co-expression network analysis, we identified 10 hub genes that were associated with the progression of CRC.

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Section: Discussionmentioning

confidence: 99%

Identification of 10 Hub genes related to the progression of colorectal cancer by co-expression analysis

Meng

Liao

et al. 2020

PeerJ

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“…Granzyme B is not only known to be produced by T cells and NK cells, but also by B cells and macrophages. 46 47 More detailed studies are required to identify the cell type(s) that produce granzyme B here. Other studies have shown that the production of granzyme B plays an important role in ECM remodeling.…”

Section: Discussionmentioning

confidence: 99%

Nicotinamide combined with gemcitabine is an immunomodulatory therapy that restrains pancreatic cancer in mice

Selvanesan

Meena

Beck

et al. 2020

J Immunother Cancer

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BackgroundTreatments for pancreatic ductal adenocarcinoma are poorly effective, at least partly due to the tumor’s immune-suppressive stromal compartment. New evidence of positive effects on immune responses in the tumor microenvironment (TME), compelled us to test the combination of gemcitabine (GEM), a standard chemotherapeutic for pancreatic cancer, with nicotinamide (NAM), the amide form of niacin (vitamin B3), in mice with pancreatic cancer.MethodsVarious mouse tumor models of pancreatic cancer, that is, orthotopic Panc-02 and KPC (KrasG12D, p53R172H, Pdx1-Cre) grafts, were treated alternately with NAM and GEM for 2 weeks, and the effects on efficacy, survival, stromal architecture and tumor-infiltrating immune cells was examined by immunohistochemistry (IHC), flow cytometry, Enzyme-linked immunospot (ELISPOT), T cell depletions in vivo, Nanostring analysis and RNAscope.ResultsA significant reduction in tumor weight and number of metastases was found, as well as a significant improved survival of the NAM+GEM group compared with all control groups. IHC and flow cytometry showed a significant decrease in tumor-associated macrophages and myeloid-derived suppressor cells in the tumors of NAM+GEM-treated mice. This correlated with a significant increase in the number of CD4 and CD8 T cells of NAM+GEM-treated tumors, and CD4 and CD8 T cell responses to tumor-associated antigen survivin, most likely through epitope spreading. In vivo depletions of T cells demonstrated the involvement of CD4 T cells in the eradication of the tumor by NAM+GEM treatment. In addition, remodeling of the tumor stroma was observed with decreased collagen I and lower expression of hyaluronic acid binding protein, reorganization of the immune cells into lymph node like structures and CD31 positive vessels. Expression profiling for a panel of immuno-oncology genes revealed significant changes in genes involved in migration and activation of T cells, attraction of dendritic cells and epitope spreading.ConclusionThis study highlights the potential of NAM+GEM as immunotherapy for advanced pancreatic cancer.

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“…This implies that, depending on the context, GrB + Bregs can instead contribute to tissue damage secondary to autoimmune inflammation. Importantly, tumor- and lymph node-infiltrating GrB + Bregs have been described in several carcinomas; however, whether GrB + Bregs are important for anti-tumoral immunity or tumor evasion remains to be further elucidated ( 385 , 398 ).…”

Section: Suppressive Mechanisms Of Bregs By Soluble Moleculesmentioning

confidence: 99%

Immunosuppressive Mechanisms of Regulatory B Cells

et al. 2021

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Regulatory B cells (Bregs) is a term that encompasses all B cells that act to suppress immune responses. Bregs contribute to the maintenance of tolerance, limiting ongoing immune responses and reestablishing immune homeostasis. The important role of Bregs in restraining the pathology associated with exacerbated inflammatory responses in autoimmunity and graft rejection has been consistently demonstrated, while more recent studies have suggested a role for this population in other immune-related conditions, such as infections, allergy, cancer, and chronic metabolic diseases. Initial studies identified IL-10 as the hallmark of Breg function; nevertheless, the past decade has seen the discovery of other molecules utilized by human and murine B cells to regulate immune responses. This new arsenal includes other anti-inflammatory cytokines such IL-35 and TGF-β, as well as cell surface proteins like CD1d and PD-L1. In this review, we examine the main suppressive mechanisms employed by these novel Breg populations. We also discuss recent evidence that helps to unravel previously unknown aspects of the phenotype, development, activation, and function of IL-10-producing Bregs, incorporating an overview on those questions that remain obscure.

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Granzyme B production by activated B cells derived from breast cancer-draining lymph nodes

Cited by 23 publications

References 21 publications

Identification of 10 Hub genes related to the progression of colorectal cancer by co-expression analysis

Identification of 10 Hub genes related to the progression of colorectal cancer by co-expression analysis

Nicotinamide combined with gemcitabine is an immunomodulatory therapy that restrains pancreatic cancer in mice

Immunosuppressive Mechanisms of Regulatory B Cells

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