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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 [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]

2023-08-01 | GSE234352 | GEO

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 [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

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

2023-08-01 | GSE229861 | GEO

Long-Term TIL Engraftment and Clonal Expansion After Multiple TIL and Anti-PD-1 Therapy: A Five-Year Immunogenomic Case Study

Project description:Adoptive cell therapy using tumor-infiltrating lymphocytes (TIL) can achieve durable responses in metastatic melanoma and other indications, but the long-term clonal dynamics after multiple administration and synergy with checkpoint blockade are still to be explored. We present a longitudinal case study of a prostate cancer patient treated with serial TIL infusions and delayed anti-PD-1 therapy, analyzed using high-throughput T-cell receptor (TCR) sequencing from serial blood and tumor samples over five years. TIL-derived clonotypes exhibited sustained persistence and clonal expansion in blood, with peaks corresponding to clinical response. Multiple TIL administration increased the patient exposure to the therapy, improving its pharmacokinetics profile over time. Notably, anti-PD-1 therapy administered six months post-first TIL administration further expanded both previously infused and novel TIL-derived clonotypes, coinciding with durable complete response. Serial tracking revealed stable levels of TIL-derived clonotypes up to five years post-treatment, with persistent tumor infiltration. T-cell clonotype expansion was associated with decreased TCR diversity and increased frequency of hyperexpanded clones, suggesting selective amplification of tumor-reactive populations. Our findings provide mechanistic insight into the long-term persistence and reactivation of TIL-derived immunity and illustrate the potent synergy between adoptive transfer and delayed PD-1 blockade, supporting the integration of longitudinal immunogenomic monitoring in personalized immunotherapy.

2025-12-04 | GSE295713 | GEO

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