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Tumor-infiltrating mast cells are associated with resistance to anti-PD-1 therapy. [RNA-Seq]

ABSTRACT: Tumor-infiltrating mast cells are associated with resistance to anti-PD-1 therapy. [RNA-Seq]

PROVIDER: PRJNA677942 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR13044112_1.fastq.gz	Fastqsanger.gz
	SRR13044112_2.fastq.gz	Fastqsanger.gz
	SRR13044113_1.fastq.gz	Fastqsanger.gz
	SRR13044113_2.fastq.gz	Fastqsanger.gz
	SRR13044114_1.fastq.gz	Fastqsanger.gz

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Tumor-infiltrating mast cells are associated with resistance to anti-PD-1 therapy. [RNA-Seq]

Project description:Increased expression of mast cell related genes in melanoma tumors obtained from humanized mice after anti-PD-1 therapy.

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Tumor-infiltrating mast cells are associated with resistance to anti-PD-1 therapy.

Project description:Tumor-infiltrating mast cells are associated with resistance to anti-PD-1 therapy.

| PRJNA677941 | ENA

Tumor-infiltrating mast cells are associated with resistance to anti-PD-1 therapy. [TCR]

Project description:Tumor-infiltrating mast cells are associated with resistance to anti-PD-1 therapy. [TCR]

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Mast cells decrease efficacy of anti-angiogenic therapy by secreting matrix-degrading granzyme B

Project description:Resistance towards anti-angiogenic therapy (AAT) still represents a substantial clinical challenge. We report here that tumor-infiltrating mast cells (MC) are powerful mediators decreasing efficacy of AAT in mice and cancer patients. They act in a cell-extrinsic manner by secreting granzyme B, which liberates pro-angiogenic mediators from the extracellular matrix. In addition, MC also diminish efficacy of anti-angiogenic agents in a cell-autonomous way, which can be blocked by the mast cell degranulation inhibitor cromolyn. Our findings are relevant in humans because patients harboring higher numbers of MC in their tumors have an inferior outcome after anti-angiogenic treatment in the Gepar Quinto randomized Phase 3 clinical trial. Thus, MC-targeting might represent a novel promising approach to increase efficacy of AAT.

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The interactions among Tumor-infiltrating T lymphocytes (TILS) induced by Stellera chamaejasme and anti-PD-1 therapy with Sing-cell Expression Profiling

Project description:Tumor-infiltrating T lymphocytes (TILS) plays a pivotal role in immunotherapy, but the dynamic relationships of the T cells reacted on the therapy remains elusive. T cell receptor (TCR) repertoire, serving as lineage tags, could track these tumor-infiltrating T lymphocytes. Here, in order to deconvolve TILS heterogeneity after therapy in a comprehensive catalog, we presented single T-cell analysis by RNA-seq and TCR tracking of a 22,590 T cells from colorectal carcinoma under control conditions and during Stellera chamaejasme and anti-PD-1 activation. We reveal a highly complex microenvironment which profoundly molds T lymphocytes, as well as the combinatorial impact of TCR utilization on phenotypic diversity. scRNA-seq identified distinct CD8 T cells subtypes CD8 naïve and CD8 cytoxic cells(CD8 CTL), also, CD4 T cell subpopulations Regulatory T(Tregs) cells and T helper cell 17(Th-17). Stellera chamaejasme activation triggered CTSW, ICOS, etc. in CD8 T cells, whose the dramatic differentiation into from a single time point. At the same time, Stellera chamaejasme plus anti-PD-1 therapy have a strikingly effect on the balance between Tregs and Th-17. Our integrated analyses provide a powerful avenue to disclose the TILS in CRC based on TCR and demonstrate novel functional interactions among TILS subpopulations during Stellera chamaejasme plus anti-PD-1 therapy.

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