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Tumor-reactive T cell clonotype dynamics underlying clinical response to TIL therapy in melanoma [multiome]

ABSTRACT: Tumor-reactive T cell clonotype dynamics underlying clinical response to TIL therapy in melanoma [multiome]

PROVIDER: PRJNA1084841 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR28245485.fastq.gz	Fastqsanger.gz
	SRR28245486.fastq.gz	Fastqsanger.gz
	SRR28245487.fastq.gz	Fastqsanger.gz

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Tumor-reactive T cell clonotype dynamics underlying clinical response to TIL therapy in melanoma [multiome]

Project description:Adoptive cell therapy (ACT) using in vitro expanded tumor-infiltrating lymphocytes (TILs) has inconsistent clinical responses. To better understand determinants of therapeutic success, we tracked TIL clonotypes from baseline tumors to ACT products and post-ACT blood and tumor samples in melanoma patients using single-cell RNA and T cell receptor (TCR) sequencing. Patients with clinical responses had baseline tumors enriched in tumor-reactive TILs, and these were more effectively mobilized upon in vitro expansion, yielding products enriched in tumor-specific CD8+ cells that preferentially infiltrated tumors post-ACT. Conversely, lack of clinical responses was associated with tumors devoid of tumor-reactive resident clonotypes and with cell products mostly composed of blood-borne clonotypes that persisted in blood but not in tumors post-ACT. Upon expansion, tumor-specific TILs lost tumor-associated transcriptional signatures, including exhaustion, and responders exhibited an intermediate exhausted effector state after TIL engraftment in the tumor, suggesting functional reinvigoration. Our findings provide insight into the nature and dynamics of tumor-specific clonotypes associated with clinical response to TIL-ACT, with implications for treatment optimization.

2024-09-13 | GSE261023 | GEO

Tumor-reactive T cell clonotype dynamics underlying clinical response to TIL therapy in melanoma

Project description:Tumor-reactive T cell clonotype dynamics underlying clinical response to TIL therapy in melanoma

| PRJNA956469 | ENA

Tumor-reactive T cell clonotype dynamics underlying clinical response to TIL therapy in melanoma [TCR-Seq]

2023-08-01 | GSE234352 | GEO

Tumor-reactive T cell clonotype dynamics underlying clinical response to TIL therapy in melanoma [scTCR-seq]

2023-08-01 | GSE229860 | GEO

Tumor-reactive T cell clonotype dynamics underlying clinical response to TIL therapy in melanoma [scRNA-seq]

2023-08-01 | GSE229858 | GEO

Tumor-reactive T cell clonotype dynamics underlying clinical response to TIL therapy in melanoma [TCR-Seq]

Project description:Tumor-reactive T cell clonotype dynamics underlying clinical response to TIL therapy in melanoma [TCR-Seq]

| PRJNA981115 | ENA

Tumor-reactive T cell clonotype dynamics underlying clinical response to TIL therapy in melanoma [scRNA-seq]

Project description:Tumor-reactive T cell clonotype dynamics underlying clinical response to TIL therapy in melanoma [scRNA-seq]

| PRJNA956475 | ENA

Tumor-reactive T cell clonotype dynamics underlying clinical response to TIL therapy in melanoma [scTCR-seq]

Project description:Tumor-reactive T cell clonotype dynamics underlying clinical response to TIL therapy in melanoma [scTCR-seq]

| PRJNA956476 | ENA

Tumor-reactive T cell clonotype dynamics underlying clinical response to TIL therapy in melanoma

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-08-01 | GSE229861 | GEO

Impaired T cell and neoantigen retention in time serial analysis of lung cancer patients treated with TIL cell therapy

Project description:Cell therapy with tumor-infiltrating lymphocytes (TIL) has yielded durable responses for multiple cancer types, but the causes of therapeutic resistance remain largely unknown. Here multi-dimensional analysis was performed on time serial tumor and blood in a lung cancer TIL therapy trial. Using T-cell receptor sequencing on both functionally expanded T cells and neoantigen-loaded tetramer-sorted T cells, we identified neoantigen specific TCRs. We then mapped clones into individual transcriptomes and found that neoantigen-reactive clonotypes expressed a dysfunctional program and lacked stem-like features among patients who lacked clinical benefit. Tracking neoantigen-reactive clonotypes over time, decay of antigen-reactive peripheral T-cell clonotypes was associated with the emergence of progressive disease. Further, subclonal neoantigens previously targeted by infused T cells were subsequently absent within tumors at progression, suggesting potential adaptive resistance. Our findings suggest that targeting clonal antigens and circumventing dysfunctional states may be important for conferring clinical responses to TIL therapy.

2024-12-30 | PXD049438 | Pride

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