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The immune system and inflammation in breast cancer.

ABSTRACT: During different stages of tumor development the immune system can either identify and destroy tumors, or promote their growth. Therapies targeting the immune system have emerged as a promising treatment modality for breast cancer, and immunotherapeutic strategies are being examined in preclinical and clinical models. However, our understanding of the complex interplay between cells of the immune system and breast cancer cells is incomplete. In this article, we review recent findings showing how the immune system plays dual host-protective and tumor-promoting roles in breast cancer initiation and progression. We then discuss estrogen receptor ? (ER?)-dependent and ER?-independent mechanisms that shield breast cancers from immunosurveillance and enable breast cancer cells to evade immune cell induced apoptosis and produce an immunosuppressive tumor microenvironment. Finally, we discuss protumorigenic inflammation that is induced during tumor progression and therapy, and how inflammation promotes more aggressive phenotypes in ER? positive breast cancers.

SUBMITTER: Jiang X

PROVIDER: S-EPMC4919022 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature

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The immune system and inflammation in breast cancer.

Jiang Xinguo X Shapiro David J DJ

Molecular and cellular endocrinology 20130619 1

During different stages of tumor development the immune system can either identify and destroy tumors, or promote their growth. Therapies targeting the immune system have emerged as a promising treatment modality for breast cancer, and immunotherapeutic strategies are being examined in preclinical and clinical models. However, our understanding of the complex interplay between cells of the immune system and breast cancer cells is incomplete. In this article, we review recent findings showing how ...[more]

PMID: 23791814

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Project description:BackgroundBreast cancer has become the malignancy with the highest mortality rate in female patients worldwide. The limited efficacy of immunotherapy as a breast cancer treatment has fueled the development of research on the tumor immune microenvironment.MethodsIn this study, data on breast cancer patients were collected from The Cancer Genome Atlas Breast Invasive Carcinoma (TCGA-BRCA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) cohorts. Differential gene expression analysis, univariate Cox regression analysis, and least absolute shrinkage and selection operator (LASSO) Cox regression analysis were performed to select overall survival (OS)-related, tumor tissue highly expressed, and immune- and inflammation-related genes. A tumor immune-inflammation signature (TIIS) consisting of 18 genes was finally screened out in the LASSO Cox regression model. Model performance was assessed by time-dependent receiver operating characteristic (ROC) curves. In addition, the CIBERSORT algorithm and abundant expression of immune checkpoints were utilized to clarify the correlation between the risk signature and immune landscape in breast cancer. Furthermore, the association of IL27 with the immune signature was analyzed in pan-cancer and the effect of IL27 on the migration of breast cancer cells was investigated since the regression coefficient of IL27 was the highest.ResultsA TIIS based on 18 genes was constructed via LASSO Cox regression analysis. In the TCGA-BRCA training cohort, 10-year AUC reached 0.89, and prediction performance of this signature was also validated in the METABRIC set. The high-risk group was significantly correlated with less infiltration of tumor-killing immune cells and the lower expression level of the immune checkpoint. Furthermore, we recommended some small-molecule drugs as novel targeted drugs for new breast cancer types. Finally, the relationship between IL27, a significant prognostic immune and inflammation cytokine, and immune status was analyzed in pan-cancer. Expression of IL27 was significantly correlated with immune regulatory gene expression and immune cell infiltration in pan-cancer. Furthermore, IL27 treatment improved breast cancer cell migration.ConclusionThe TIIS represents a promising prognostic tool for estimating OS in patients with breast cancer and is correlated with immune status.

Project description:Post-partum uterine inflammation (endometritis) is associated with lower fertility at both the time of infection and after the inflammation has resolved. It was hypothesized that aberrant DNA methylation may be involved in the sub-fertility associated with post-partum uterine inflammation. The objective of this study was to characterize genome-wide DNA methylation and gene expression in the endometrium of dairy cows with sub-clinical endometritis. Endometrial tissues were obtained at 29 days post-partum (n=12) and Agilent two-colour microarrays were used to characterize transcription and DNA methylation profiles. Analyses revealed 1,856 probes to be differentially expressed in animals with subclinical endometritis (SUI, n=6) compared with control cows (NUI, n=6, P<0.05, Storey Multiple testing correction). No significant associations among DNA methylation and gene expression were detected. Further analysis of gene expression data using GeneGo Metacore and Gene Set Enrichment Analysis identified several pathways and processes enriched in the comparison. Several pathways that are involved in the innate immune response were enriched in SUI cows. Consistent with the presence of microorganisms in the uterus, there was enrichment for the Toll-like receptor (TLR) signaling pathway, including increased expression of the transcription factor NFKB1, the pro-inflammatory cytokines IL1A and IL1B, downstream chemokines, cytokines, and acute phase and antimicrobial proteins in the endometrium of SUI cows. Furthermore, the chemokine signaling pathway was enriched in SUI cows, with increased expression of genes that attract cells of the innate immune system. Increased expression of IL-8 and CXCL6, chemotactic factors for recruitment of neutrophils along with the immune cell surface marker PTPRC in SUI cows is consistent with the greater number of polymorphonuclear cells present in the uterus of these cows. Several antimicrobial peptides (LAP, TAP, DEFB1, DEFB10, DEFB103B, DEFB7) and acute phase proteins, including SAA3, LBP, and the complement gene CFB, had greater expression in SUI cows. Gene expression profiles in cows with subclinical endometritis in this study indicate that the immune response is activated, potentially resulting in a local pro-inflammatory environment in the uterus. If this period of inflammation is prolonged, it could result in tissue damage or failure to complete involution of the uterus, which may create a sub-optimal environment for future pregnancy. 12 animals were enrolled in this study, 2 samples from each animal were used for microarray analysis consisting of caruncular and intercaruncular endometrium. A reference design was used for hybridisation, whereby each of the 24 samples were hybridised to individual microarrays along with a pooled reference sample. The reference sample was generated by taking equal concentrations of each of the experimental samples.

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The immune system and inflammation in breast cancer.

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The immune system and inflammation in breast cancer.

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