The DOI matches its Crossref record; 51 of the 52 references it cites were found in a registry or an index.
Adaptive Immune Resistance Emerges from Tumor-Initiating Stem Cells
Open accessAbstract
Our bodies are equipped with powerful immune surveillance to clear cancerous cells as they emerge. How tumor-initiating stem cells (tSCs) that form and propagate cancers equip themselves to overcome this barrier remains poorly understood. To tackle this problem, we designed a skin cancer model for squamous cell carcinoma (SCC) that can be effectively challenged by adoptive cytotoxic T cell transfer (ACT)-based immunotherapy. Using single-cell RNA sequencing (RNA-seq) and lineage tracing, we found that transforming growth factor β (TGF-β)-responding tSCs are superior at resisting ACT and form the root of tumor relapse. Probing mechanism, we discovered that during malignancy, tSCs selectively acquire CD80, a surface ligand previously identified on immune cells. Moreover, upon engaging cytotoxic T lymphocyte antigen-4 (CTLA4), CD80-expressing tSCs directly dampen cytotoxic T cell activity. Conversely, upon CTLA4- or TGF-β-blocking immunotherapies or Cd80 ablation, tSCs become vulnerable, diminishing tumor relapse after ACT treatment. Our findings place tSCs at the crux of how immune checkpoint pathways are activated.
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“The latter possibility is consistent with TSKs resembling tumor-initiating stem cells better equipped to survive adoptive cytotoxic T cell therapy in a mouse model of cSCC (Miao et al., 2019).”
From Multimodal Analysis of Composition and Spatial Architecture in Human Squamous Cell Carcinoma (2020) · cites this paper as Miao et al., 2019
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TGFβ attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells
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1 of the 52 references couldn’t be matched to a known paper.
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Tumour-intrinsic resistance to immune checkpoint blockade
Kalbasi, A. K., & Ribas, A. (2019) · Nature reviews. Immunology · doi:10.1038/s41577-019-0218-4 · Cited by 1,525
Multimodal Analysis of Composition and Spatial Architecture in Human Squamous Cell Carcinoma
Ji, A. L., Rubin, A. J., Thrane, K., Jiang, S., Reynolds, D. L., Meyers, R. M., Guo, M. G., George, B. M., Mollbrink, A., Bergenstråhle, J., et al. (2020) · Cell · doi:10.1016/j.cell.2020.05.039 · Cited by 1,117
“The latter possibility is consistent with TSKs resembling tumor-initiating stem cells better equipped to survive adoptive cytotoxic T cell therapy in a mouse model of cSCC (Miao et al., 2019).”
ResultIntratumoral heterogeneity in cancer progression and response to immunotherapy
Vitale, I., Shema, E., Loi, S., & Galluzzi, L. (2021) · Nature Medicine · doi:10.1038/s41591-021-01233-9 · Cited by 848
Clara, J., Monge, C., Yang, Y., & Takebe, N. (2019) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-019-0293-2 · Cited by 768
Cancer stem cell–immune cell crosstalk in tumour progression
Bayık, D., & Lathia, J. D. (2021) · Nature reviews. Cancer · doi:10.1038/s41568-021-00366-w · Cited by 564
Metadata
- Authors
- Miao, Y., Yang, H., Levorse, J., Yuan, S., Polak, L., Sribour, M., Singh, B., Rosenblum, M. D., & Fuchs, E.
- Affiliations
- Howard Hughes Medical Institute (US)
- Memorial Sloan Kettering Cancer Center (US)
- University of California, San Francisco (US)
- Corresponding author
- Fuchs, Elaine
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2019-05
- Volume
- 177
- Issue
- 5
- Pages
- 1172-1186.e14
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC6525024
- OpenAlex
- W2942376604
- Cited by
- 299
- References
- 52
- Citations by year
- 2026: 29 · 2025: 35 · 2024: 43 · 2023: 51 · 2022: 36 · 2021: 49 · 2020: 41 · 2019: 15
- FWCI
- 14.73
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Jane Coffin Childs Memorial Fund for Medical Research
- National Institutes of Health (R01-AR050452, R- 01AR27883, C32585GG)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- adaptive immune resistance, squamous cell carcinoma, skin cancer, TGF-beta, CD80, CTLA-4, immune checkpoint, tumor recurrence, immune evasion, cancer stem cells
- MeSH terms
- Animals, Carcinoma, Squamous Cell, Humans, Immunity, Cellular, Immunologic Surveillance, Mice, Transgenic, Neoplasm Proteins, Skin Neoplasms, T-Lymphocytes, Neoplastic Stem Cells, Adoptive Transfer, Cell Line, Tumor, Mice
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