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Heme-TAMs are resistant to tumoricidal transformation by INFγ

ABSTRACT: Heme-TAMs are resistant to tumoricidal transformation by INFγ

PROVIDER: PRJNA993273 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR25223820.fastq.gz	Fastqsanger.gz
	SRR25223821.fastq.gz	Fastqsanger.gz
	SRR25223822.fastq.gz	Fastqsanger.gz
	SRR25223823.fastq.gz	Fastqsanger.gz
	SRR25223824.fastq.gz	Fastqsanger.gz

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Heme-TAMs are resistant to tumoricidal transformation by INFγ

Project description:Inflammatory macrophage activation is a critical component of the antitumor immune response and an emerging therapeutic concept. To evaluate the impact of heme exposure on antitumoral macrophage activity, we grew spheroids of mixed GFP-MC38 and BMDMs that were either untreated or pretreated with heme, INFγ, or heme + INFγ, and characterized them by scRNA-seq.

2024-01-03 | GSE236996 | GEO

Mixed cell-type spheroids endorse the generation and maintenance of heme-TAMs in an experimental tumor microenvironment [joint analysis]

Project description:Within the tumor microenvironment, heme exposure drives the transformation of macrophages into Arg1high Spp1high heme-TAMs with an enhanced matrix remodeling program and suppressed immunity, resisting inflammatory rewiring by INFγ and LPS.

2024-01-15 | GSE237257 | GEO

Heme-signaling progresses via NRF2 to educate heme-TAM transformation, tumor cell growth, and invasiveness

Project description:Heme-activation of NRF2 is a strong anti-inflammatory signal in macrophages, and analyses in this study indicated that the expressed transcriptome in heme-TAMs was consistently enriched for NRF2 target genes. We have therefore delineated the role of NRF2 in a series of experiments with Nrf2 knockout BMDMs, leading to a locked NRF2-inactive state, and macrophages with a knockout of the cytoplasmic NRF2 capture protein KEAP1, leading to a locked NRF2-active state, irrespective of the presence or absence of heme. To demonstrate that activated NRF2 is sufficient to drive heme-TAM transformation, we analyzed Keap1 knockout macrophages.

2024-01-03 | GSE236997 | GEO

Heme-TAMs prevent cancer cell apoptosis and drive growth, invasiveness, and metastasis

Project description:To study the impact of heme-TAMs on the growth, phenotype, and function of cancer cells, we cultured GFP-MC38 cells either alone or mixed with heme-treated macrophages in microwell plates, enabling us to collect large numbers of uniform spheroids for scRNA-seq. We observed that after four days, the size of GFP-MC38 spheroids regressed, and the tumor cells underwent apoptosis and decayed metabolically. In contrast, the presence of heme-TAMs within spheroids prevented apoptosis, supporting the extended growth of metabolically viable spheroids beyond 10 days of culture.

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Heme-TAMs prevent cancer cell apoptosis and drive growth, invasiveness, and metastasis

Project description:Heme-TAMs prevent cancer cell apoptosis and drive growth, invasiveness, and metastasis

| PRJNA993275 | ENA

Heme-signaling progresses via NRF2 to educate heme-TAM transformation, tumor cell growth, and invasiveness

Project description:Heme-signaling progresses via NRF2 to educate heme-TAM transformation, tumor cell growth, and invasiveness

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The effect of imatinib therapy on tumor associated macrophages (TAMs) in human gastrointestinal stromal tumor (GIST)

Project description:The gene expression profile of TAMs microbead isolated from freshly obtained human GISTs were compared in tumors that were untreated, responding to imatinib (sensitive), or resistant to imatinib (resistant) The Affymetrix Human Genome U133A 2.0 platform was used TAMs were microbead isolated from 12 untreated, 5 sensitive, and 4 resistant tumors. Tumors were obtained freshly from the operating room from consenting patients using an IRB approved protocol. Tumors were digested using collagenase and TAMs isolated using microbead negative selection for KIT, CD3, and CD56 followed by positive selection for CD14.

2013-11-20 | E-GEOD-51697 | biostudies-arrayexpress

Mixed cell-type spheroids endorse the generation and maintenance of heme-TAMs in an experimental tumor microenvironment

Project description:To more accurately mimic the tumor microenvironment, we established a three-dimensional culture of MC38 cancer cells mixed with heme-treated BMDMs in microwell plates. This resulted in tumor spheroids with uniformly interspersed macrophages. We profiled the transcriptome of macrophages within these spheroids using scRNA-seq 24 hours after spheroid formation. To test the robustness of the heme effects in this model, we conducted a multiplexed experiment evaluating heme alone and in combination with the classical M1-polarization stimuli INFγ and LPS.

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Mixed cell-type spheroids endorse the generation and maintenance of heme-TAMs in an experimental tumor microenvironment

Project description:Mixed cell-type spheroids endorse the generation and maintenance of heme-TAMs in an experimental tumor microenvironment

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Gene expression profiles of tumor-associated macrophages (TAMs) overexpressing miR-511-3p

Project description:Hematopoietic stem/progenitor cells (HS/PCs) were transduced with lentiviral vectors overexpressing OFP and either miR-511-3p or a control, mutated miRNA sequence (miR-511-3p-mut). The transduced HS/PCs were then transplanted in recipient C57BL/6 mice. Tumors (Lewis lung carcinomas, LLC) were injected s.c. 4 weeks after HS/PC transplant. Lentiviral vector-transduced (OFP+), tumor-associated macrophages (TAMs) were isolated 4 weeks after LLC injection by fluorescence-activated cell sorting. Gene expression profiles of TAMs overexpressing either miR-511-3p or miR-511-3p-mut were obtained from 3 independent biological samples/each. Gene expression profiles of miRNA-overexpressing TAMs were then compared with the gene expression profiles of wild-type TAMs isolated from LLCs grown in nontransplanted C57BL/6 mice; the latter TAMs were subfractioned into MRC1+CD11c(low) or CD11c+MRC1(low) subsets before RNA isolation and analysis. Comparison of gene expression profiles of TAMs revealed that miR-511-3p overexpression tunes down the expression of multiple genes that are classically upregulated in protumoral MRC1+CD11c(low) TAMs. TAMs were isolated from Lewis lung carcinomas grown s.c. in C57BL/6 mice.

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