Eosinophils restrict CRC metastasis by inhibiting pro-tumorigenic Spp1+ macrophage differentiation.
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ABSTRACT:
PROVIDER: PRJNA1190381 | ENA |
REPOSITORIES: ENA
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Project description:Eosinophils, traditionally associated with allergic responses, have emerged as critical immune modulators in colorectal cancer (CRC). Here, we reveal that eosinophils actively shape the tumor microenvironment and influence metastatic progression. Using comprehensive transcriptomics analysis of human CRC and a murine orthotopic tumor model, we identify a conserved tumor-specific eosinophil signature and activation profile. Despite their declining presence in advanced CRC, eosinophils suppress metastatic dissemination by counteracting the pro-tumorigenic functions of SPP1+ macrophages – a subset linked to immune exclusion and tumor metastasis. Mechanistically, eosinophils respond to tumor-derived signals and inhibit macrophage differentiation into SPP1+ cells. Eosinophil depletion exacerbates peritoneal tumor spread. These findings highlight the pivotal role of eosinophils in restraining late-stage CRC progression and unveil a novel eosinophil–macrophage axis as potential therapeutic targets.
2024-12-17 | GSE282765 | GEO
Project description:The recognition of the immune system as a key component of the tumor microenvironment (TME) led to promising therapeutics. Since such therapies benefit only subsets of patients, understanding the activities of immune cells in the TME is required. Eosinophils are an integral part of the TME especially in mucosal tumors. Nonetheless, their role in the TME and the environmental cues that direct their activities are largely unknown, especially in metastasis. We report that breast cancer-driven lung metastasis is characterized by resident and recruited eosinophils. Eosinophil recruitment to the metastatic lung was regulated by G protein coupled receptor signaling but independent of CCR3. Functionally, eosinophils promoted lymphocyte-mediated anti tumor immunity. Transcriptome and proteomic analyses identified the TME rather than intrinsic differences between eosinophil subsets as a key instructing factor directing anti tumorigenic eosinophil activities. Specifically, TNF-a/IFN-g-activated eosinophils facilitated CD4+ and CD8+ T cell infiltration and promoted anti-tumor immunity. Collectively, we identify a mechanism by which the TME entrains eosinophils to adopt anti-tumorigenic properties, which may lead to the development of eosinophil-targeted therapeutics.
2021-07-27 | PXD027596 | Pride
Project description:The recognition of the immune system as a key component of the tumor microenvironment (TME) led to promising therapeutics. Since such therapies benefit only subsets of patients, understanding the activities of immune cells in the TME is required. Eosinophils are an integral part of the TME especially in mucosal tumors.Nonetheless, their role in the TME and the environmental cues that direct their activities are largely unknown, especially in metastasis. We report that breast cancer-driven lung metastasis is characterized by resident and recruited eosinophils. Eosinophil recruitment to the metastatic lung was regulated by G protein coupled receptor signaling but independent of CCR3. Functionally, eosinophils promoted lymphocyte-mediated anti53 tumor immunity. Transcriptome and proteomic analyses identified the TME rather than intrinsic differences between eosinophil subsets as a key instructing factor directing anti tumorigenic eosinophil activities. Specifically, TNF-a/IFN-g-activated eosinophils facilitated CD4+ and CD8+ T cell infiltration and promoted anti-tumor immunity. Collectively, we identify a mechanism by which the TME entrains eosinophils to adopt anti-tumorigenic properties, which may lead to the development of eosinophil-targeted therapeutics.
2021-08-06 | GSE181491 | GEO
Project description:Eosinophils are present in several solid tumors and have context-dependent function. The role of eosinophils in the development of esophageal squamous cell cancer (ESCC), 85% of esophageal cancers worldwide, is unknown. Mice were treated with 4-nitroquinolone-1-oxide (4-NQO) for 8 weeks followed by vehicle for 8 weeks to induce esophageal squamous pre-cancer. Eosinophil depletion using three mouse models resulted in exacerbated 4-NQO tumorigenesis. In order to study the transcriptional profiles of eosinophils specifically, we isolated eosinophils from esophageal tissue of WT mice which had been treated with 4-NQO in the pre-cancer model. Because eosinophils are not present in the esophagus normally, we isolated eosinophils from the colons of a random subset of the same mice. Additionally, we derived eosinophils from the bone marrow of a random subset of the same mice.
2023-12-01 | GSE233448 | GEO
Project description:Arabidopsis thaliana CRC, Transcription factor CRC [Source:UniProtKB/TrEMBL;Acc:Q1PFF1], is differentially expressed in 11 experiment(s);
| AT1G69180 | ExpressionAtlas
Project description:Arabidopsis thaliana CRC, Transcription factor CRC [Source:UniProtKB/TrEMBL;Acc:Q1PFF1], is expressed in 8 baseline experiment(s);
| AT1G69180 | ExpressionAtlas
Project description:Arabidopsis thaliana CRC, 12S seed storage protein CRC [Source:UniProtKB/Swiss-Prot;Acc:Q96318], is expressed in 8 baseline experiment(s);
| AT4G28520 | ExpressionAtlas
Project description:Arabidopsis thaliana CRC, 12S seed storage protein CRC [Source:UniProtKB/Swiss-Prot;Acc:Q96318], is differentially expressed in 37 experiment(s);
| AT4G28520 | ExpressionAtlas
Project description:Eosinophils are present in several solid tumors and have context-dependent function. The role of eosinophils in the development of esophageal squamous cell cancer (ESCC), 85% of esophageal cancers worldwide, is unknown. Mice were treated with 4-nitroquinolone-1-oxide (4-NQO) for 8 weeks followed by vehicle for 8 weeks to induce esophageal squamous pre-cancer. Eosinophil depletion using three mouse models resulted in exacerbated 4-NQO tumorigenesis. RNA-sequencing on the whole esophagus of WT and ?dblGATA mice was done in the pre-cancer model to understand how the presence of eosinophils affects the pre-cancer esophageal environment.
2023-12-01 | GSE233443 | GEO
Project description:Bacillus Calmette-Guerin (BCG) therapy is an established immunotherapy for non-muscle invasive bladder cancer (NMIBC); however, the response variability of patients remains a challenge, necessitating insight into immune cell function. Previous studies established that a preexisting Th2 immune microenvironment correlates with a positive BCG therapy outcome. Therefore, in this study, we explored the role of mast cells (MCs) and eosinophils in bladder cancer as a potential predicting tool for BCG immunotherapy response. Methods: We investigated the effect of MCs and eosinophils on bladder cancer cell viability together with their chemotactic migration towards cancer cells in vitro. The effect of BCG on these immune cells was also evaluated. Moreover, we performed an orthotopic model of bladder cancer in MC- and eosinophil-deficient mice. Finally, to evaluate whether these immune cells predict the therapy response, 26 patient biopsies pre-BCG treatment were analyzed for MC and eosinophil numbers in the tissue and 11 among them were sequenced for gene expression. Results: Eosinophils, but not MCs, reduced bladder cancer cell viability in vitro and inhibited tumor growth in vivo. However, addition of BCG did not increase these effects in vitro. Patient biopsy analysis and mRNA sequencing showed that neither cell type predicted long-term therapy responsiveness. Gene expression analysis suggested that extracellular matrix and epithelial-to-mesenchymal transition factors could influence BCG therapy outcomes. Conclusion: Even though eosinophils exhibit anti-tumorigenic effects in bladder cancer, neither MCs nor eosinophils were predictive of the long-term BCG therapy response. However, our findings implicate that matrix-related factors may modulate BCG therapy responses.
2025-04-30 | GSE291192 | GEO