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Tumor intrinsic activity of Chromobox 2 (CBX2) remodels the tumor microenvironment in high grade serous carcinoma

ABSTRACT: Tumor intrinsic activity of Chromobox 2 (CBX2) remodels the tumor microenvironment in high grade serous carcinoma

PROVIDER: PRJNA1055961 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR27330208_1.fastq.gz	Fastqsanger.gz
	SRR27330208_2.fastq.gz	Fastqsanger.gz
	SRR27330209_1.fastq.gz	Fastqsanger.gz
	SRR27330209_2.fastq.gz	Fastqsanger.gz
	SRR27330210_1.fastq.gz	Fastqsanger.gz

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Tumor intrinsic activity of Chromobox 2 (CBX2) remodels the tumor microenvironment in high grade serous carcinoma

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Tumor-Intrinsic Activity of Chromobox 2 Remodels the Tumor Microenvironment in High-grade Serous Carcinoma.

Project description:Chromobox 2 (CBX2), an epigenetic reader and component of polycomb repressor complex 1, is highly expressed in >75% of high-grade serous carcinoma. Increased CBX2 expression is associated with poorer survival, whereas CBX2 knockdown leads to improved chemotherapy sensitivity. In a high-grade serous carcinoma immune-competent murine model, knockdown of CBX2 decreased tumor progression. We sought to explore the impact of modulation of CBX2 on the tumor immune microenvironment (TIME), understanding that the TIME plays a critical role in disease progression and development of therapy resistance. Exploration of existing datasets demonstrated that elevated CBX2 expression significantly correlated with specific immune cell types in the TIME. RNA sequencing and pathway analysis of differentially expressed genes demonstrated immune signature enrichment. Confocal microscopy and co-culture experiments found that modulation of CBX2 leads to increased recruitment and infiltration of macrophages. Flow cytometry of macrophages cultured with CBX2-overexpressing cells showed increased M2-like macrophages and decreased phagocytosis activity. Cbx2 knockdown in the Trp53-null, Brca2-null ID8 syngeneic murine model (ID8 Trp53-/-Brca2-/-) led to decreased tumor progression compared with the control. NanoString immuno-oncology panel analysis suggested that knockdown in Cbx2 shifts immune cell composition, with an increase in macrophages. Multispectral immunohistochemistry (mIHC) further confirmed an increase in macrophage infiltration. Increased CBX2 expression leads to recruitment and polarization of protumor macrophages, and targeting CBX2 may serve to modulate the TIME to enhance the efficacy of immune therapies.SignificanceCBX2 expression correlates with the TIME. CBX2 modulation shifts the macrophage population, potentially leading to an immunosuppressive microenvironment, highlighting CBX2 as a target to improve efficacy of immunotherapy.

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Project description:CBX2 knockdown in the PEO1 high grade serous cell line

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Cbx2

Project description:Rattus norvegicus Cbx2, chromobox 2 [Source:RGD Symbol;Acc:1588561], is expressed in 4 baseline experiment(s);