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Response to tumor- infiltrating lymphocyte adoptive therapy is associated with preexisting CD8+T- myeloid cell networks in melanoma

ABSTRACT: Response to tumor- infiltrating lymphocyte adoptive therapy is associated with preexisting CD8+T- myeloid cell networks in melanoma

PROVIDER: PRJNA922112 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR22803300_1.fastq.gz	Fastqsanger.gz
	SRR22803300_2.fastq.gz	Fastqsanger.gz
	SRR22803301_1.fastq.gz	Fastqsanger.gz
	SRR22803301_2.fastq.gz	Fastqsanger.gz
	SRR22803302_1.fastq.gz	Fastqsanger.gz

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Response to tumor- infiltrating lymphocyte adoptive therapy is associated with preexisting CD8+T- myeloid cell networks in melanoma [scTCRseq]

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Response to tumor- infiltrating lymphocyte adoptive therapy is associated with preexisting CD8+T- myeloid cell networks in melanoma [scTCRseq]

Project description:Adoptive cell therapy (ACT) using ex vivo–expanded tumor-infiltrating lymphocytes (TILs) can eliminate or shrink metastatic melanoma, but its long-term efficacy remains limited to a fraction of patients. Using longitudinal samples from 13 patients with metastatic melanoma treated with TIL-ACT in a phase 1 clinical study, we interrogated cellular states within the tumor microenvironment (TME) and their interactions. We performed bulk and single-cell RNA sequencing, whole-exome sequencing, and spatial proteomic analyses in pre- and post-ACT tumor tissues, finding that ACT responders exhibited higher basal tumor cell–intrinsic immunogenicity and mutational burden. Compared with nonresponders, CD8+ TILs exhibited increased cytotoxicity, exhaustion, and costimulation, whereas myeloid cells had increased type I interferon signaling in responders. Cell-cell interaction prediction analyses corroborated by spatial neighborhood analyses revealed that responders had rich baseline intratumoral and stromal tumor–reactive T cell networks with activated myeloid populations. Successful TIL-ACT therapy further reprogrammed the myeloid compartment and increased TIL-myeloid networks. Our systematic target discovery study identifies potential T-myeloid cell network–based biomarkers that could improve patient selection and guide the design of ACT clinical trials.

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Response to tumor- infiltrating lymphocyte adoptive therapy is associated with preexisting CD8+T- myeloid cell networks in melanoma [full scRNAseq]

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