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NanoSTRING analysis of sorted intratumoral CD8+ T cells following radiotherapy

ABSTRACT: NanoSTRING analysis of sorted intratumoral CD8+ T cells following radiotherapy

PROVIDER: PRJNA853748 | ENA |

REPOSITORIES: ENA

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NanoSTRING analysis of sorted intratumoral CD8+ T cells following radiotherapy

Project description:The recruitment of monocytes and their differentiation into immunosuppressive cells is associated with the negative outcome of non-conformal radiotherapy (RT). However, non-conformal RT is irrelevant in the clinic, and little is known about the role of monocytes following radiotherapy modes used in patients, such as conformal radiotherapy (CRT). Here, we investigated the acute immune infiltration post-CRT. Contrary to non-conformal RT approaches, we found that CRT induces a rapid and robust recruitment of monocytes to the tumor that minimally differentiate into tumor-associated macrophages (TAM) or dendritic cells (DC), but instead upregulate major histocompatibility complex II (MHCII) and costimulatory molecules. We establish that these large numbers of infiltrating monocytes are responsible for increasing type I interferon in the tumor microenvironment (TME), activation of CD8+ T cells and the reduction in tumor burden. Importantly, we demonstrate that rapid monocyte infiltration to the TME is hindered when RT inadvertently affects healthy tissues. Our results unravel a positive role of monocytes during clinically relevant modes of RT and demonstrate that limiting exposure of healthy tissues to radiation has a positive therapeutic effect on the overall immune response within the tumor. The objective of this experiment was to evaluate the transcriptional changes in CD8+ T cells following different modes of radiation at 3 days post treatment

2023-05-07 | GSE207105 | GEO

Pre-existing intratumoral stem-like CD8+ T-Cells drive radiotherapy-induced tumor control

Project description:To evaluate how intratumoral CD8+ T-cells are influenced by radiotherapy, we performed single-cell RNA sequencing of CD8+ T-cells sorted from MC38-OVA tumors 6 days after radiotherapy (single dose, 20Gy).

2025-03-24 | GSE279242 | GEO

NanoSTRING analysis of sorted monocytes/monoACT cells following radiotherapy

Project description:NanoSTRING analysis of sorted monocytes/monoACT cells following radiotherapy

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NanoSTRING analysis of sorted monocytes/monoACT cells following radiotherapy

Project description:The recruitment of monocytes and their differentiation into immunosuppressive cells is associated with the negative outcome of non-conformal radiotherapy (RT). However, non-conformal RT is irrelevant in the clinic, and little is known about the role of monocytes following radiotherapy modes used in patients, such as conformal radiotherapy (CRT). Here, we investigated the acute immune infiltration post-CRT. Contrary to non-conformal RT approaches, we found that CRT induces a rapid and robust recruitment of monocytes to the tumor that minimally differentiate into tumor-associated macrophages (TAM) or dendritic cells (DC), but instead upregulate major histocompatibility complex II (MHCII) and costimulatory molecules. We establish that these large numbers of infiltrating monocytes are responsible for increasing type I interferon in the tumor microenvironment (TME), activation of CD8+ T cells and the reduction in tumor burden. Importantly, we demonstrate that rapid monocyte infiltration to the TME is hindered when RT inadvertently affects healthy tissues. Our results unravel a positive role of monocytes during clinically relevant modes of RT and demonstrate that limiting exposure of healthy tissues to radiation has a positive therapeutic effect on the overall immune response within the tumor. The objective of this experiment was to evaulate the transcriptional changes in monocytes following different modes of radiation at 3 days post treatment

2023-05-07 | GSE223400 | GEO

Pre-existing intratumoral stem-like CD8+ T-Cells drive radiotherapy-induced tumor control

Project description:Pre-existing intratumoral stem-like CD8+ T-Cells drive radiotherapy-induced tumor control

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RNA Sequencing of Intratumoral Immune Populations in Pancreatic Ductal Adenocarcinoma Following Radiotherapy and Interleukin 12 Treatment

Project description:We report differential gene expression in inflammatory monocyte (IM), tumor-associated macrophage (TAM), and CD8 T cell populations following stereotactic body radiation (SBRT), intratumoral interleukin 12 microsphere (IL-12 MS) delivery, and SBRT/IL-12 MS combination. Immune cell populations were sorted from orthotopic murine pancreatic ductal adenocarcinoma (PDA) tumors prior to RNA sequencing.

2020-04-14 | GSE136368 | GEO

RNA Sequencing of Intratumoral Immune Populations in Pancreatic Ductal Adenocarcinoma Following Radiotherapy and Interleukin 12 Treatment

Project description:RNA Sequencing of Intratumoral Immune Populations in Pancreatic Ductal Adenocarcinoma Following Radiotherapy and Interleukin 12 Treatment

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Transcriptional differences between intratumoral CD8+ T cells in young and aged tumors at single cell resolution

Project description:Single-cell RNA sequencing of intratumoral CD8+ T cells (and CD45+ cells) from young and aged mice

2024-03-14 | GSE255373 | GEO

SERT inhibits CD8 T cell antitumor immunity through regulating the intratumoral serotonin axis

Project description:Identifying new immune checkpoint molecules hindering antitumor T cell responses and devising new therapeutic blockades are key to the development of next-generation cancer immunotherapies. Here, we report the induction of the serotonin transporter (SERT) in solid tumor-infiltrating cytotoxic CD8 T cells, a molecule best known for its role in regulating serotonin neurotransmission in the brain. In solid tumors, CD8 T cells secrete serotonin, which stimulates their antitumor reactivities, while SERT functions as a negative regulator by depleting intratumoral serotonin. Inhibition of SERT using clinically approved selective serotonin reuptake inhibitors (SSRIs), a popular class of antidepressants, significantly suppressed tumor growth and enhanced CD8 T cell-mediated antitumor responses in various preclinical mouse syngeneic and human xenograft tumor models. Importantly, SSRI treatment exhibited significant therapeutic synergy with anti-PD-1 therapy, and clinical data correlation studies negatively associated intratumoral SERT expression with patient survival in a range of cancers. These findings highlight the significance of the intratumoral serotonin axis and identify SERT as a novel immune checkpoint, positioning SSRIs as promising candidates for next-generation combination cancer therapies.

2025-05-27 | GSE262781 | GEO

Intratumoral mregDC and Tfh-like niches enable local reinvigoration of CD8 T cells following PD-1 blockade

Project description:While T cell accumulation in tumors is associated with response to immune checkpoint blockade (ICB), many T cell-rich tumors fail to respond to ICB. Here we leveraged a large neoadjuvant PD-1 blockade trial in hepatocellular carcinoma (HCC) to search for correlates of ICB response within T cell-rich tumors. Paired scRNAseq/TCRseq of nearly one million immune cells revealed that tumor responses to ICB correlated with significant clonal expansion of intratumoral CH25H+CXCL13+IL-21+CD4 T cells and GranzymeK+PD-1+CD8 effector T cells, whereas terminally exhausted CD39hiToxhiPD-1hi CD8 clones dominated in non-responders. Notably, proliferating and progenitor CD8 T cells clones were found in tumors of responders and non-responders. However, tumors from responders were highly enriched in mregDCs, a DC state triggered by capture of tumor debris, which formed physically interacting cellular triads with Tfh-like CD4 and progenitor-like CD8 T cells. Receptor-ligand analysis revealed unique interactions within these triads that may promote progenitor CD8 T cell differentiation into effector cells upon PD-1 blockade. These results suggest that discrete cellular niches that include mregDCs and Tfh-like CD4 T cells might control the differentiation of tumor-specific progenitor CD8 T cell clones into effective anti-tumor T cells in human tumors.

2023-06-16 | GSE206325 | GEO

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