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Tumor-infiltrating monocytic myeloid-derived suppressor cells contribute to the development of an immunosuppressive tumor microenvironment in gastric cancer

ABSTRACT: Tumor-infiltrating monocytic myeloid-derived suppressor cells contribute to the development of an immunosuppressive tumor microenvironment in gastric cancer

PROVIDER: PRJNA830909 | ENA |

REPOSITORIES: ENA

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			Action	DRS
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	SRR18898300.fastq.gz	Fastqsanger.gz
	SRR18898301.fastq.gz	Fastqsanger.gz
	SRR18898302.fastq.gz	Fastqsanger.gz
	SRR18898303.fastq.gz	Fastqsanger.gz

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Tumor-infiltrating monocytic myeloid-derived suppressor cells contribute to the development of an immunosuppressive tumor microenvironment in gastric cancer

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Tumor-infiltrating monocytic myeloid-derived suppressor cells contribute to the development of an immunosuppressive tumor microenvironment in gastric cancer

Project description:The present study suggests that TI-M-MDSCs, especially IER3+ ones, may play a predominant role in the development of the immunosuppressive and ICI-resistant GC TIME.

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Project description:Immune checkpoint inhibitors (ICIs) have improved outcomes in advanced cancers, yet resistance remains a major obsticle. Here, we investigated the role of myeloid cells in shaping the immunosuppressive tumor microenvironment that contributes to ICI resistance. Using mutagenized ICI-sensitive and resistant 4T1 breast cancer clones, we performed single-cell RNA sequencing to characterize immune cell populations post-ICI therapy. We identified monocytic dendritic progenitors (MDPs) and common monocytic progenitors (cMOPs) enriched in sensitive tumors, which may differentiate into immunosuppressive cells in resistant tumors. Analysis of public datasets confirmed the presence of MDP-cMOPs in tumors and blood of breast, lung, and colorectal cancer patients. We found high expression of CXCR4 and IL6R in MDP-cMOPs, and inhibiting these pathways blocked their recruitment and differentiation. Combined targeting of CXCR4 and IL6 pathway with ICI improved responses in resistant tumors, highlighting MDP-cMOPs as contributors to immunotherapy resistance and potential therapeutic targets.

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Project description:Analysis of MDSC subsets from naive blood and RMA-S blood and RMA-S tumor, respectively. Tumor-infiltrating MO-MDSCs changed their expression pattern compared to blood and exhibited high levels of chemokines Total RNA obtained from PMN-MDSCs and MO-MDSCs from naive blood or from blood and tumor of RMA-S bearing mice

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Heme oxygenase-1 orchestrates the immunosuppressive program of tumor-associated macrophages [ATAC-Seq]

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Heme oxygenase-1 orchestrates the immunosuppressive program of tumor-associated macrophages [RNA-Seq]

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