Evaluation of triple negative breast cancer with heterogeneous immune infiltration
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PROVIDER: EGAS00001007159 | EGA |
REPOSITORIES: EGA
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Project description:CD95 suppresses immune infiltration in a model of triple negative breast cancer
| PRJNA647186 | ENA
Project description:Triple-negative breast cancer represents approximately 15–20% of all reported breast cancer cases, and is characterized by a shorter survival time and higher mortality rates compared to other breast cancer sub-types. Tumor microenvironment (TME) refers to the internal and external environment of tumor tissue. Increasing evidence indicates that a tumor’s microenvironment is tightly associated with the immunological surveillance and defense during the development of breast cancer. Although oncology studies employing digital dissection methodologies have provided some insight on the biological features of TME, the development of methods to investigate the cellular composition of the tumor microenvironment remain an important research priority. In this study, we extracted whole transcriptome from 30 Triple-negative breast cancer (TNBC) patients and then used bioinformatics approaches to characterize cell type content in tumor tissue compared with para-cancerous tissue. We identified 4 types of enriched immune cells and 6 types of downregulated immune cells in the tumor tissue samples. After comprehensive bioinformatics analyses, we developed an ‘immune infiltration score’ (IIS) to quantitatively model immune cell infiltration in TNBC. To demonstrate the utility of the IIS, we used 2 independent datasets for validation. We found that patients with a higher IIS showing a longer progression-free survival time and significantly better prognosis than those with a lower IIS value. In sum, we explored the immune infiltration landscape in 30 TNBC patients and provided a novel and reliable biomarker IIS to evaluate the progression-free survival and prognosis in the TNBC patients.
2021-10-18 | E-MTAB-10886 | biostudies-arrayexpress
Project description:ImportanceWhy some triple-negative breast cancers (TNBCs) have high and others have low immune cell infiltration is unknown. Understanding how immune surveillance shapes the cancer genome could help in the selection of patients and the development of more effective immunotherapy strategies.ObjectiveTo examine the association between genomic metrics and the extent of immune infiltration in TNBCs.Design, setting, and participantsThis study, performed from June 1, 2015, through January 31, 2017, used DNA and RNA sequencing data and messenger RNA expression results from The Cancer Genome Atlas (TCGA) breast cancer data set (n = 1215) to calculate previously described immune metagene expression values and histologic lymphocyte counts to quantify immune infiltration and assign prognostic categories to TNBCs. It used the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) data set as an independent validation cohort. The study compared clonal heterogeneity, somatic total mutational load, neoantigen load, and somatic copy number alteration levels between immune-rich TNBC cohorts with good prognosis and immune-poor TNBC cohorts with poor prognosis. The study also compared the distribution of mutations in 119 canonical cancer genes.Main outcomes and measuresCorrelation between immune prognostic category and genomic metrics of the cancer.ResultsThis study of 193 TNBC samples with patient survival information found an inverse association between clonal heterogeneity and immune metagene expression (ρ = −0.395, P = 2 × 10−8). The study also found an inverse association between immune metagene expression and somatic copy number alteration levels (ρ = −0.484, P = 2 × 10−10). Lymphocyte-rich TNBCs with good prognosis had significantly lower mutation and neoantigen counts than did lymphocyte-poor TNBCs with poor prognosis. The robustness of the study results was confirmed by using various immune metagenes in the same TCGA data set and in the independent METABRIC data set.Conclusions and relevanceThis study suggests that immune-rich TNBCs may be under an immune surveillance that continuously eliminates many immunogenic clones, resulting in lower clonal heterogeneity. These cancers may also represent the subset of TNBCs that could derive benefit from immune checkpoint inhibitor therapy to tilt the balance in favor of the immune system.
| S-EPMC5824276 | biostudies-literature
Project description:Immune Infiltration in Aggressive Papillary Craniopharyngioma: High infiltration But Low Action
| PRJNA892989 | ENA
Project description:The Immunoscore is a method to quantify the immune cell infiltration within cancers to predict the disease prognosis. Previous immune profiling approaches relied on limited immune markers to establish patients’ tumor immunity. However, immune cells exhibit a higher-level complexity that is typically not obtained by the conventional immunohistochemistry methods. Herein, we present a spatially variant immune infiltration score, termed as SpatialVizScore, to quantify immune cells infiltration within lung tumor samples using multiplex protein imaging data. Imaging mass cytometry (IMC) was used to target 26 markers in tumors to identify stromal, immune, and cancer cell states within 26 human tissues from lung cancer patients. Unsupervised clustering methods dissected the spatial infiltration of cells in tissue using the high-dimensional analysis of 16 immune markers and other cancer and stroma enriched labels to profile alterations in the tumors’ immune infiltration patterns. Spatially resolved maps of distinct tumors determined the spatial proximity and neighborhoods of immune-cancer cell pairs. These SpatialVizScore maps provided a ranking of patients’ tumors consisting of immune inflamed, immune suppressed, and immune cold states, demonstrating the tumor’s immune continuum assigned to three distinct infiltration score ranges. Several inflammatory and suppressive immune markers were used to establish the cell-based scoring schemes at the single-cell and pixel-level, depicting the cellular spectra in diverse lung tissues. Thus, SpatialVizScore is an emerging quantitative method to deeply study tumor immunology in cancer tissues.
2022-10-14 | PXD035340 | Pride
Project description:CD95 acts as an immune suppressor for TNBC tumors when grown in syngeneic mice. 4T1 cells were grown in two mouse strains. Comparisons included parental, a pool stably expressing vCas9 and two clones in which CD95/Fas was deleted using CRISPR-Cas9 gene editing, clone #54 and clone #69.
2020-07-20 | GSE154682 | GEO
Project description:In patients with triple-negative breast cancer (TNBC), tumor-infiltrating lymphocytes (TILs) are associated with improved survival. Lehmann et al. identified 4 molecular subtypes of TNBC [basal-like (BL) 1, BL2, mesenchymal (M), and luminal androgen receptor (LAR)], and an immunomodulatory (IM) gene expression signature indicates the presence of TILs and modifies these subtypes. The association between TNBC subtype and TILs is not known. Also, the association between inflammatory breast cancer (IBC) and the presence of TILs is not known. Therefore, we studied the IM subtype distribution among different TNBC subtypes. We retrospectively analyzed patients with TNBC from the World IBC Consortium dataset. The molecular subtype and the IM signature [positive (IM+) or negative (IM-)] were analyzed. Fisher's exact test was used to analyze the distribution of positivity for the IM signature according to the TNBC molecular subtype and IBC status. There were 88 patients with TNBC in the dataset, and among them 39 patients (44%) had IBC and 49 (56%) had non-IBC. The frequency of IM+ cases differed by TNBC subtype (p = 0.001). The frequency of IM+ cases by subtype was as follows: BL1, 48% (14/29); BL2, 30% (3/10); LAR, 18% (3/17); and M, 0% (0/21) (in 11 patients, the subtype could not be determined). The frequency of IM+ cases did not differ between patients with IBC and non-IBC (23% and 33%, respectively; p = 0.35). In conclusion, the IM signature representing the underlying molecular correlate of TILs in the tumor may differ by TNBC subtype but not by IBC status.
| S-EPMC6193579 | biostudies-literature
Project description:Chemokines and their receptors are key players in breast cancer progression and outcome. Previous studies have shown that the chemokine receptor CXCR2 was expressed at higher levels by cells of the tumor microenvironment in triple-negative breast cancers (TNBCs). The aim of this study was to focus our attention on a retrospective cohort of 290 TNBC cases and analyze the involvement of CXCR2, CD11b (a marker of granulocytes) and CD66b (a marker of neutrophils) and their link with immune infiltration and immune checkpoint markers. We report that high densities of CXCR2-, CD11b- and CD66b-positive cells were associated with high-grade tumors. Moreover, molecular apocrine TNBCs, defined here as tumors that express both AR and FOXA1 biomarkers, exhibited low levels of CXCR2 and CD11b. High CXCR2 and CD11b levels were correlated with elevated density of tumor-infiltrating lymphocytes (TILs), CD8+ cytotoxic lymphocytes, expression of PD-L1 by tumor and stromal cells and of PD-1 by stromal cells. On the other hand, CD66b levels were associated only with CD8+, stromal PD-L1 and PD-1 expression. In univariate analysis, low levels of CXCR2 were correlated with poor OS and RFS. In multivariate analysis, low levels of CXCR2 were associated with poor OS. Finally, in TNBC treated with adjuvant chemotherapy, CXCR2 density was associated with longer RFS. Overall, our data highlight the potential beneficial association of high levels of CXCR2 with a subgroup of TNBC patients characterized by a better prognosis.
| S-EPMC8151934 | biostudies-literature
Project description:Papillary craniopharyngiomas (PCPs) are biologically benign but clinically aggressive lesions hence affect the quality of life. The expression of inflammatory mediators and regulation of the immune microenvironment in PCPs have not been investigated much. In this study, for the first time, we assessed the immune cell infiltration and immune cell signatures in PCPs by analyzing the bulk-RNA sequencing data. Our results indicated that PCPs are in a state of high immune infiltration but low action with abundant inflammatory cells.
2022-10-28 | GSE216330 | GEO
Project description:Breast cancer represents the number one cause of cancer-associated mortality globally. The most aggressive molecular subtype is triple negative breast cancer (TNBC), of which limited therapeutic options are available. It is well known that breast cancer prognosis and tumor sensitivity toward immunotherapy are dictated by the tumor microenvironment. Breast cancer gene expression profiles were extracted from the METABRIC dataset and two TNBC clusters displaying unique immune features were identified. Activated immune cells formed a large proportion of cells in the high infiltration cluster, which correlated to a good prognosis. Differentially expressed genes (DEGs) extracted between two heterogeneous subtypes were used to further explore the underlying immune mechanism and to identify prognostic biomarkers. Functional enrichment analysis revealed that the DEGs were predominately related to some processes involved in activation and regulation of innate immune signaling. Using network analysis, we identified two modules in which genes were selected for further prognostic investigation. Validation by independent datasets revealed that CXCL9 and CXCL13 were good prognostic biomarkers for TNBC. We also performed comparisons between the above two genes and immune markers (CYT, APM, TILs, and TIS), as well as cell checkpoint marker expressions, and found a statistically significant correlation between them in both METABRIC and TCGA datasets. The potential of CXCL9 and CXCL13 to predict chemotherapy sensitivity was also evaluated. We found that the CXCL9 and CXCL13 were good predictors for chemotherapy and their expressions were higher in chemotherapy-responsive patients in contrast to those who were not responsive. In brief, immune infiltrate characterization on TNBC revealed heterogeneous subtypes with unique immune features allowed for the identification of informative and reliable characteristics representative of the local immune tumor microenvironment and were potential candidates to guide the management of TNBC patients.
| S-EPMC8017297 | biostudies-literature