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

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

PROVIDER: PRJNA981115 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR24865914.fastq.gz	Fastqsanger.gz
	SRR24865915.fastq.gz	Fastqsanger.gz
	SRR24865916.fastq.gz	Fastqsanger.gz
	SRR24865917.fastq.gz	Fastqsanger.gz
	SRR24865918.fastq.gz	Fastqsanger.gz

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

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.

2023-08-01 | GSE234352 | GEO

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

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

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

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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

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

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

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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

Peripheral blood TCR clonotype diversity as an age-associated marker of breast cancer progression (TCR)

Project description:Immune escape is a prerequisite of tumor growth. We previously described a decline in intratumor activated GZMB+CD8+ T cells and T cell receptor (TCR) clonotype diversity in invasive compared to in situ (DCIS) breast carcinomas implying a role for decreasing TCR diversity in tumor progression. Here, we evaluated peripheral blood TCR clonotype diversity in breast cancer patients diagnosed with DCIS or de novo stage IV disease at different ages. We found that peripheral TCR diversity is associated with clinicopathologic, and peripheral immune status and it correlates with the frequency of CD8+ T cells in DCIS of young patients. These results provide new insights to the role of host immunity and breast cancer development in different aged women.

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ATLAS-seq: a novel microfluidic single-cell TCR screen for highly reactive antigen-specific TCRs

Project description:Clonotype selection of T cell receptors (TCRs) have been the core component of TCR therapy development. However, the conventional and widely used major histocompatibility complex (MHC) multimer staining technologies focus on high-affinity interactions between TCR and MHC-antigen complex, which may fail to identify TCRs with high efficacy for activating T cells. Here, we developed the Aptamer-based T Lymphocyte Activity Screening and sequencing (ATLAS-seq) method on a microfluidic platform. ATLAS-seq isolates and characterizes activated T cells using an aptamer-based fluorescent molecular sensor to monitor cytokine secretion from single-T cells upon antigen stimulation, followed by single-cell sequencing. As a proof of principle study, we used ATLAS-seq to screen cytomegalovirus (CMV)-reactive TCRs and identified a distinct clonotype population with a higher T cell activation level compared to one recovered by Dextramer staining method. Furthermore, we observed that ATLAS-seq selected TCR clonotypes are more efficient in target cell killing than those from Dextramer staining. Therefore, our ATLAS-seq can provide an efficient workflow to screen highly reactive antigen-specific TCR clonotypes for cancer immunotherapy.

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