Effect of carcinogen exposure on gene expression of tumor-associated macrophages
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE237536 | GEO | 2023/09/12
REPOSITORIES: GEO
Similar Datasets
Project description:Chemotherapies have been shown to enhance anti-tumor immunity, but whether chemotherapies affect tumor-associated macrophages (TAMs) is still unclear. We found TAMs is different before and after chemotherapy by comparing proteomic profiles of TAMs before and after chemotherapy.
2021-02-16 | PXD022673 | Pride
Project description:Murine macrophages: Peritoneal exudate macrophages (PECs) vs tumor-associated macrophages (TAMs)
| PRJNA704618 | ENA
Project description:Chemotherapies have been shown to enhance anti-tumor immunity, but whether chemotherapies affect tumor-associated macrophages (TAMs) is still unclear. We found TAMs is different before and after chemotherapy by comparing proteomic profiles of TAMs before and after chemotherapy.
2021-02-16 | PXD022674 | Pride
Project description:Colorectal cancer is a major cause of mortality worldwide. Most patients develop colorectal liver metastases (CLM), and for such patients hepatectomy combined with chemotherapy may be curative. Nevertheless, in the era of precision medicine there is a critical need of prognostic markers to cope with the heterogeneity of CLM patients. Tumor-associated macrophages (TAMs) pave the way to tissue invasion and intravasation providing a nurturing microenvironment formetastases. The quantification of immune landscape of tumors has provided novel prognostic indicators of cancer progression, and the quantification of TAMs might explain the heterogeneity of CLM patients. Here, we will investigate the development of a new diagnostic tool based on TAMs with the aim to define the causative role of TAMs in CLM patients. This will open new clinical scenarios both for the diagnosis, therapy and prognosis, leading to the refinement of the therapeutic output in a personalized medicine perspective.
| 2300850 | ecrin-mdr-crc
Project description:Macrophages have been implicated in breast cancer progression and metastasis, but relatively little is known about the genes and pathways that are involved. Using a conditional allele of Ets2 in the mouse, we have identified Ets2 as a critical gene in tumor associated macrophages (TAMs) that specifically promotes mammary tumor metastasis. Loss of Ets2 in TAMs decreased the frequency and size of lung metastases without impacting primary tumor burden. Expression profiling of isolated tumor macrophages established that Ets2 deficiency resulted in the de-repression of a defined set of anti-angiogenic genes. Activation of this transcriptional program correlated with decreased angiogenesis in metastatic tumors and decreased metastatic growth. Comparison of this Ets2-specific TAM expression profile with human breast cancer profiles revealed a macrophage gene expression signature that could predict overall survival of estrogen receptor negative patients. In summary, we have identified a critical factor, Ets2, in TAMs that represses a transcriptional program to promote the growth of mammary tumor metastases in the lung. Breast TAMs were isolated from early-stage PyMT-induced mammary tumors expressing Ets2 and also from the tumors with Ets2-deficient TAMs. Since macrophages have also been implicated in normal mammary gland remodeling, normal remeodeling macrophages were also purified from females expressing Ets2 and the ones where Ets2 is deleted in the macrophages. One RNA sample was extracted from each genetic group for gene-expression profiling.
2010-01-05 | E-GEOD-12863 | biostudies-arrayexpress
Project description:Active immunotherapy is a promising strategy for anti-angiogenic cancer therapy. Recently, we have reported that a vaccine using human umbilical vein endothelial cells (HUVECs) induced specific anti-endothelial immune responses in the most of immunized patients, and resulted in tumor regression in some patients with recurrent malignant brain tumors, whereas not in colorectal cancer patients. In this study, we hypothesized that non-hypoxic perivascular tumor associated macrophages (TAMs) in colorectal cancer, but not in glioblastoma, might negatively alter the therapeutic efficacy of anti-angiogenic active immunotherapy. To test this hypothesis, we examined global gene expression profiles of non-hypoxic macrophages stimulated in vitro by soluble factors released from tumor cells of human glioblastoma U-87MG (‘brain TAMs’) or colorectal adenocarcinoma HT-29 (‘colon TAMs’). Murine non-hypoxic TAMs were induced in vitro by incubation with soluble factors released from human cancer cell lines U-87MG ('brain TAMs') or HT-29 ('colon TAMs'), for RNA extraction and subsequent hybridization on Affymetrix microarrays. To evaluate homogeneous macrophage populations at different tumour developmental stages, RNA aliquots of control macrophages and TAMs obtained at five different time-points, i.e. 8h, 16h, 24h, 32h and 40h, were pooled and used for screening of differentially expressed genes. The experiments for TAMs as well as for control unstimulated macrophages were performed in triplicates.
2012-03-31 | E-GEOD-18804 | biostudies-arrayexpress
Project description:Activating CD8+ T cells by antigen cross-presentation is remarkably effective at eliminating tumors. Although this function is traditionally attributed to dendritic cells, tumor-associated macrophages (TAMs) can also cross-present antigens. TAMs are the most abundant tumor-infiltrating leukocyte. Yet, TAMs have not been leveraged to activate CD8+ T cells because mechanisms that modulate their ability to cross-present antigens are incompletely understood. Here we show that TAMs harbor hyperactive cysteine protease activity in their lysosomes which impedes antigen cross-presentation, thereby preventing CD8+ T cell activation. We developed a DNA nanodevice (E64-DNA) targeted to lysosomes of TAMs in mice. E64-DNA inhibits the population of cysteine proteases present specifically inside lysosomes of TAMs, improves their ability to cross-present antigens, and attenuates tumor growth via CD8+ T cells. When combined with cyclophosphamide, E64-DNA showed sustained tumor regression in a triple-negative-breast-cancer model. Our studies demonstrate that DNA nanodevices can be targeted with organelle-level precision to reprogram macrophages and achieve immunomodulation in vivo.
2021-10-14 | PXD028037 | Pride
Project description:Tumor-immune cell interactions shape the immune cell phenotype, with microRNAs (miRs) being crucial components of this crosstalk. How they are transferred, and how they affect their target landscape, especially in tumor-associated macrophages (TAMs), is largely unknown. Here we aimed to define miRome of TAMs and identify novel miRs those are deferentially expression in TAMs and decipher their functional relevance in disease settings.
2019-02-08 | E-MTAB-6885 | biostudies-arrayexpress
Project description:Tumor associated macrophages show signs of both, classical pro-inflammatory as well as alternative macrophage activation. The aim of this study was to compare TAMs across tumor types, to characterize their phenotype in detail and to identify the signaling nodules involved regulating classical and alternative activation traits. To identify gene expression profiles and pathways differentially activated in tumor-associated macrophages (TAMs) we isolated TAMs from in vivo animal models of EG7 thymoma (n=3), glioma (n=3) and neuroblastoma (n=3) by tumor digestion and subsequent enrichment of CD11b+ cells using Miltenyi magnetic beads. Thymomas grown in WT or Myd88-/- mice (n=5 per group) were used to identify TLR/IL1R dependent signaling in TAMs. RNA extracted from CD11b+ TAMs was analyzed using the Affymetrx HT_MG-430_PM arrays. For in-depth analysis of the role of inflammatory signaling by TNFR1 (Tnfrsf1a) and/or Myd88, EG7 TAM populations A (CD11b+, Ly6G-, Ly6C+, MHCII-) and C (CD11b+, Ly6C-, MHCII+) were isolated by flow cytometric sorting from WT, TNFR1-/-, Myd88flox/flox; Tie2-Cre and TNFR-/-; Myd88flox/flox; Tie2-cre mice and extracted RNA was analyzed by microarray using the Mouse Gene 2.0 GeneChip arrays (n=2 per genotype and population).
2015-04-28 | E-GEOD-59047 | biostudies-arrayexpress
Project description:Tumor-associated macrophages (TAMs) shape tumor immunity and therapeutic efficacy. However, it is poorly understood if and how post-translational modifications (PTMs) intrinsically affect the phenotype and function of TAMs. Here, we found that peptidylarginine deiminase 4 (PAD4) manifested the highest expression among common PTM enzymes in TAMs and negatively correlated to clinical response to immune checkpoint blockade (ICB). Genetic and pharmacological inhibition of PAD4 in macrophages prevented tumor progression in tumor-bearing mouse models, accompanied by an increase in macrophage MHC-II expression and T-cell effector function. Mechanistically, PAD4 citrullinated STAT1 at arginine 121 (R121), thereby promoting the interaction between STAT1 and PIAS1; and the loss of PAD4 abolished this interaction, ablating the inhibitory role of PIAS1 in the expression of MHC-II machinery in macrophages and enhancing T-cell activation. Thus, the PAD4-STAT1-PIAS1 axis is a previously unknown intrinsic immune restriction mechanism in macrophages and may serve as a cancer immunotherapy target.
2024-05-22 | PXD049188 | Pride