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In situ tumor arrays reveal early environmental control of cancer immunity [STAMP D8]

ABSTRACT: In situ tumor arrays reveal early environmental control of cancer immunity [STAMP D8]

PROVIDER: PRJNA917336 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR22952434.fastq.gz	Fastqsanger.gz
	SRR22952435.fastq.gz	Fastqsanger.gz
	SRR22952436.fastq.gz	Fastqsanger.gz
	SRR22952437.fastq.gz	Fastqsanger.gz
	SRR22952438.fastq.gz	Fastqsanger.gz

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In situ tumor arrays reveal early environmental control of cancer immunity [STAMP D8]

Project description:KPP-GFP (C57Bl/6) cells were implanted into the laser-induced micropores ears of B6.Cg-Foxn1nu/J (C57Bl/6J Jackson background) that were adoptively transferred with 4x10^6 naive CD4tdTomato-positive Tcells (B6 N/J background) the same day. The STAMP microtumors were imaged daily starting at day 3 after tumor cell implantation. On day 8 after tumor cell implantation tumors were classified as either (1) Inflamed, (2) Excluded, (3) Ignored/Desert or (4) Resolved.

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Project description:The immune phenotype of a tumor is a key predictor of its response to immunotherapy1–4. Patients who respond to immune checkpoint blockade generally present with tumors infiltrated by T cells, a phenotype referred to as ‘inflamed’5–7. However, not all inflamed tumors respond to therapy, and even lower response rates occur among patients with tumors that lack T cells (‘desert’) or that spatially exclude T cells to the periphery of the tumor lesion (‘excluded’)8. Despite the importance of these tumor immune phenotypes in patients, little is known about their development, heterogeneity or dynamics due to the technical difficulty of modeling and tracking these features in situ. Here, we introduce STAMP (skin tumor array by microporation), a preclinical approach that combines in vivo high-throughput time-lapse imaging with next generation sequencing of tumor arrays. Using this approach, we follow the early formation of thousands of tumors to show that development of a given immune phenotype is not under strict control of tumor genetics or transcriptional state, but is also influenced by local features of the tumor microenvironment. Only the spatial organization of T cells, specifically early infiltration of T cells recruited by fibroblasts and monocytes into the core of a tumor, was predictive of functional T cell attack and tumor rejection. Evaluating the dynamic immune-history of tumors revealed that early conversion to the immune inflamed phenotype was predictive of therapy-induced or spontaneous tumor regression. Thus, STAMP captures the dynamic and complex relationships of spatial, cellular and molecular components of tumor progression and has the potential to translate therapeutic concepts into successful clinical strategies.

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Project description:The STAMP tumor model utilizes laser-guided microporation to deposit tumor cells into the dermis of the mouse ear. This project is aimed to characterize the early molecular and cellular changes associated with microporation and tumor cell seeding along the time course of 8 days in WT C57Bl6 animals. The data generated in this project will allow us to decipher which changes are associated with microporation and how it compares to the tumor progression.

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