Tumor microenvironment participates in metastasis of pancreatic cancer

Ren, Bo; Cui, Ming; Ye, Gang; Wang, Huanyu; Feng, Mengyu; You, Lei; Zhao, Yupei

doi:10.1186/s12943-018-0858-1

Cited by 446 publications

(371 citation statements)

References 170 publications

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“…[70][71][72] Cancer cells tend to upregulate the activity of co-inhibitory signaling pathways to escape immune surveillance. 73,74 Immune checkpoint inhibitors (ICIs) alleviate immune tolerance to tumor antigens and reinvigorate the antitumor response. Anti-PD-1/PD-L1 and anti-CTLA-4 have been successfully applied in multiple cancers.…”

Section: Immune Checkpoint Inhibitormentioning

confidence: 99%

Manipulating Gut Microbiota Composition to Enhance the Therapeutic Effect of Cancer Immunotherapy

Jiao

Qin

et al. 2019

Integr Cancer Ther

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In the past decade, a growing set of immunotherapies including immune checkpoint blockade, chimeric antigen receptor T cells, and bispecific antibodies propelled the advancement of oncology therapeutics. Accumulating evidence demonstrates that immunotherapy could eliminate tumors better than traditional chemotherapy or radiotherapy with lower risk of adverse events in numerous cancer types. Unfortunately, a substantial proportion of patients eventually acquire resistance to immunotherapy. By analyzing the differences between immunotherapy-sensitive and immunotherapy-resistant populations, it was noticed that the composition of gut microbiota is closely related to treatment effect. Moreover, in xenograft models, interventional regulation of gut microbiota could effectively enhance efficacy and relieve resistance during immunotherapy. Thus, we believe that gut microbiota composition might be helpful to explain the heterogeneity of treatment effect, and manipulating gut microbiota could be a promising adjuvant treatment for cancer immunotherapy. In this mini review, we focus on the latest understanding of the cross-talk between gut microbiota and host immunity. Moreover, we highlight the role of gut microbiota in cancer immunotherapy including immune checkpoint inhibitor and adoptive cell transfer.

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Section: Immune Checkpoint Inhibitormentioning

confidence: 99%

Manipulating Gut Microbiota Composition to Enhance the Therapeutic Effect of Cancer Immunotherapy

Jiao

Qin

et al. 2019

Integr Cancer Ther

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“…Accumulating evidences suggest that molecular components of the TME modulate cancer progression (Incio et al, 2016;Ren et al, 2018). CAFs, a key component of the TME, play major roles in supporting cancer progression (Gascard & Tlsty, 2016;Karagiannis et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

Extra domain A‐containing fibronectin expression in Spin90‐deficient fibroblasts mediates cancer‐stroma interaction and promotes breast cancer progression

Kwon

Chae

You

et al. 2019

Journal Cellular Physiology

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Cancer-associated fibroblasts (CAFs) in the tumor microenvironment play major roles in supporting cancer progression. A previous report showed that SPIN90 downregulation is correlated with CAF activation and that SPIN90-deficient CAFs promote breast cancer progression. However, the mechanisms that mediate cancer-stroma interaction and how such interactions regulate cancer progression are not well understood. Here, we show that extra domain A (EDA)-containing fibronectin (FN), FN(+)EDA, produced by mouse embryonic fibroblasts (MEFs) derived from Spin90knockout (KO) mice increases their own myofibroblast differentiation, which facilitates breast cancer progression. Increased FN(+)EDA in Spin90-KO MEFs promoted fibril formation in the extracellular matrix (ECM) and specifically interacted with integrin α4β1 as the mediating receptor. Moreover, FN(+)EDA expression by Spin90-KO MEFs increased proliferation, migration, and invasion of breast cancer cells. Irigenin, a specific inhibitor of the interaction between integrin α4β1 and FN(+) EDA, significantly blocked the effects of FN(+)EDA, such as fibril formation by Spin90-KO MEFs and proliferation, migration, and invasion of breast cancer cells. In orthotopic breast cancer mouse models, irigenin injection remarkably reduced tumor growth and lung metastases. It was supported by that FN(+)EDA in assembled fibrils was accumulated in cancer stroma of human breast cancer patients in which SPIN90 expression was downregulated. Our data suggest that SPIN90 downregulation increases FN(+)EDA and promotes ECM stiffening in breast cancer stroma through an assembly of long FN(+)EDA-rich fibrils; moreover, engagement of the Integrin α4β1 receptor facilitates breast cancer progression. Inhibitory effects of irigenin on tumor growth and metastasis suggest the potential of this agent as an anticancer therapeutic. K E Y W O R D S cancer-associated fibroblast, extracellular matrix, FN(+)EDA, SPIN90, tumor microenvironment Breast cancer tissues with adjacent normal epithelial tissues of Human patients were kindly supplied and analyzed by Chungbuk

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“…Previous studies showed that CD4 + T cells, CD8 + T cells and macrophages played important roles in the TME and tumor prognosis. In pancreatic tumor tissues, the higher proportions of CD4 + and CD8 + T cells, the better long-term prognosis for patients [40]. In breast carcinoma, annexin1 promoted polarization of M1 macrophages and induced pro-inflammatory genes [41].…”

Section: Kinase Targets Of Hub Genesmentioning

confidence: 99%

Identification of genes with therapeutic and prognostic values in lung adenocarcinoma microenvironment

Jiang¹,

Gao²,

Zhang³

et al. 2020

Preprint

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Background As the most diagnosed malignancy, lung cancer is also the primary cause of cancer death in the entire world. The therapy of lung adenocarcinoma (LUAD), which is the most prevalent subtype of lung cancer, draw researchers’ increasing attentions. This research aimed to investigate the tumor microenvironment (TME)-related hub genes which might be novel targets for treatment. Materials and methods LUAD-associated data packages, including RNA-Seq information and clinical data of 522 patients, were obtained from The Cancer Genome Atlas (TCGA). For better evaluation of stromal and immune cell components, immune scores, stromal scores and estimate scores were obtained with ESTIMATE algorithm based on gene expression levels in tumors. The R package heatmap and clustering analysis were used to explore interested genes. Differentially expressed genes (DEGs) were identified by Venn diagram. Protein-protein interaction (PPI) network was applied to explore intrinsic connections of DEGs. Kaplan-Meier (K-M) survival curves, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were applied to investigate the prognostic values and intricate biological functions of DEGs. The relationships between 4 survival-related hub genes and 6 types of immune cells were examined using TIMER database. The LinkedOmics database was applied to look for kinase targets of hub genes. Results The immune/stromal/estimate scores were significantly correlated with clinical features, including the grades and sizes of LUAD, distant metastasis and outcomes. A total of 702 DEGs, 589 up-regulated and 113 down-regulated, were identified. GO and KEGG analysis showed that the DEGs had significant correlations with tumor immunology. PPI network suggested that the top 8 nodes were FPR2, C3AR1, MCHR1, CCR5, FPR1, CCL19, CCR2 and CXCL10. K-M survival curves indicated that FPR2, C3AR1, MCHR1 and CCR5, as hub genes, were significantly correlated with the overall survival (OS) of LUAD patients. The expression levels of C3AR1 and CCR5 were positively correlated with immune cell infiltration. LYN, LCK and SYK were the targeted kinases of these hub genes. Conclusion FPR2, C3AR1, MCHR1 and CCR5 were TME-related genes and potential biomarkers for the therapy and prognosis of LUAD.

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Tumor microenvironment participates in metastasis of pancreatic cancer

Cited by 446 publications

References 170 publications

Manipulating Gut Microbiota Composition to Enhance the Therapeutic Effect of Cancer Immunotherapy

Manipulating Gut Microbiota Composition to Enhance the Therapeutic Effect of Cancer Immunotherapy

Extra domain A‐containing fibronectin expression in Spin90‐deficient fibroblasts mediates cancer‐stroma interaction and promotes breast cancer progression

Identification of genes with therapeutic and prognostic values in lung adenocarcinoma microenvironment

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