Data · dataset · 2022
Colorectal cancer interleukin-10 blockade scRNA-seq
Listed in DataCite
Objective: PD-1 checkpoint inhibition and adoptive cellular therapy have limited success in patients with microsatellite stable colorectal cancer liver metastases (CRLM).
Description
We demonstrate that interleukin-10 (IL-10) blockade enhances endogenous T cell and chimeric antigen receptor T (CAR-T) cell anti-tumor function in CRLM slice cultures.Design: We created organotypic slice cultures from human CRLM (n = 38) and tested the anti-tumor effects of a neutralizing antibody against IL-10 (αIL-10).
We evaluated slice cultures with single and multiplex immunohistochemistry, in situ hybridization, single cell RNA sequencing, and time-lapse fluorescent microscopy. In addition, we studied the effects of αIL-10 on carcinoembryonic antigen (CEA)-specific CAR-T cells exogenously administered to both human CRLM slice cultures and a CRLM murine model. Results: There was little effect of PD-1 blockade in CRLM slice cultures.
Read the rest (2 more)
In contrast, αIL-10 generated 1.8-fold increase in T cell-mediated carcinoma cell death, and increased proportion of CD8+ T cells and inflammatory polarization of macrophages. In addition to effects on endogenous immune cells in human CRLM, αIL-10 also rescued murine CAR-T cell proliferation and cytotoxicity from myeloid cell-mediated immunosuppression. In human CRLM slices, αIL-10 dramatically improved CEA-specific CAR-T cell cytotoxicity, generating nearly 70% carcinoma apoptosis across multiple human tumors.
We saw a less dramatic, but similar effect of pretreatment of CAR-T cells with an IL-10 receptor blocking antibody, demonstrating that IL-10 inhibits CAR-T function in the CRLM tumor microenvironment. Conclusion: Neutralizing the effects of IL-10 in human CRLM has therapeutic potential as a stand-alone treatment and to augment the function of adoptively transferred CAR-T cells.
Links
Where it is published
- Repository landing page datadryad.org/dataset/doi:10.5061/dryad.0cfxpnw54 ↗
landing page · from DataCite
- DOI doi.org/10.5061/dryad.0cfxpnw54 ↗
DOI / persistent id · from DataCite
Documentation and papers
- Creative Commons Zero v1.0 Universal creativecommons.org/publicdomain/zero/1.0/legalcode ↗
license · from DataCite
- IsCitedBy 10.1136/gutjnl-2021-325808 doi.org/10.1136/gutjnl-2021-325808 ↗
publication · from DataCite
Catalogue records · 2
- DataCite API api.datacite.org/dois/10.5061/dryad.0cfxpnw54 ↗
metadata API · from DataCite
- DataCite Commons commons.datacite.org/doi.org/10.5061/dryad.0cfxpnw54 ↗
catalogue entry · from DataCite
Topics
- Stated by source
- Basic medicine
- Inferred from text
- Cancer 75% · Microscopy 75% · RNA sequencing 75% · Sequencing 75% · Single-cell RNA sequencing 65%
Provenance · 1 source records, 13 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| DataCite | 10.5061/dryad.0cfxpnw54 | 14 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · DataCite | connector:datacite@1.0.0 | /data/attributes/rightsList |
| byte_size | source · DataCite | connector:datacite@1.0.0 | |
| concepts[disease].local:disease:cancer | enrichment · DataCite | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[field].fos:basic-medicine | source · DataCite | connector:datacite@1.0.0 | |
| concepts[modality].local:modality:microscopy | enrichment · DataCite | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[modality].local:modality:rna-seq | enrichment · DataCite | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[modality].local:modality:sequencing | enrichment · DataCite | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[modality].local:modality:single-cell-rna-seq | enrichment · DataCite | keyword-concept-rules@1.0.0 | title+description (65%) |
| description | source · DataCite | connector:datacite@1.0.0 | /data/attributes/descriptions |
| license | source · DataCite | connector:datacite@1.0.0 | /data/attributes/rightsList |
| publication_date | source · DataCite | connector:datacite@1.0.0 | /data/attributes/dates |
| title | source · DataCite | connector:datacite@1.0.0 | /data/attributes/titles/0/title |
| version_label | source · DataCite | connector:datacite@1.0.0 |