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Biological Sciences - Article
Martin Prlic
Fred Hutchinson Cancer Research Center
Corresponding Author
ORCiD: https://orcid.org/0000-0002-0685-9321
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Immunotherapies to treat cancer have achieved remarkable successes, but major challenges persist. An inherent weakness of current treatment approaches is that therapeutically targeted pathways are not only found in tumors, but also in tissue microenvironments, particularly inflamed tissues. This confounding overlap complicates treatment as well as predictions of treatment outcome. In an effort to identify potential tumor-unique immunotherapeutic targets that are distinct from general tissue inflammation, we used complementary single-cell analysis approaches to interrogate immune cell alterations and interactions in human squamous cell carcinomas and site-matched non-malignant, inflamed tissues. We found that a distinct population of intratumoral regulatory T cells (Tregs) received T cell receptor (TCR) signals from antigen-presenting cells and this Treg population was uniquely identified by co-expression of ICOS and IL-1 receptor type 1 (IL-1R1). Intratumoral IL-1R+ Tregs appeared activated and a TCR signal was sufficient to convert IL-1R1- Tregs to IL-1R1+ Tregs ex vivo. Overall, our work identifies an intratumoral Treg population that recognizes antigen in the tumor microenvironment and two biomarkers that allow for specific depletion of these Tregs. Finally, our approach also provides a blueprint for extricating tumor-unique therapeutic targets distinct from general inflammatory patterns in other tumors.
Keywords
immunotherapies, cancer, inflammation
Yes there is potential Competing Interest. R.G. has received speaker fees from Illumina and Fluidigm and support from Juno Therapeutics and Janssen Pharma, has consulted for Takeda Vaccines, Juno Therapeutics and Infotech Soft, and has ownership interest in CellSpace Bio. E.G. declares ownership interest in Ozette Technologies. F.M, J.R.E and M.P. are holding the related patent “Specific Targeting of Tumor-infiltrating regulatory T cells (Tregs) using ICOS and IL-1R1” (US patent #63/092957).
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A new preprint design is coming!
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This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Biological Sciences - Article
Martin Prlic
Fred Hutchinson Cancer Research Center
Corresponding Author
ORCiD: https://orcid.org/0000-0002-0685-9321
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 1
Posted 17 May, 2021
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Immunology
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Immunotherapies to treat cancer have achieved remarkable successes, but major challenges persist. An inherent weakness of current treatment approaches is that therapeutically targeted pathways are not only found in tumors, but also in tissue microenvironments, particularly inflamed tissues. This confounding overlap complicates treatment as well as predictions of treatment outcome. In an effort to identify potential tumor-unique immunotherapeutic targets that are distinct from general tissue inflammation, we used complementary single-cell analysis approaches to interrogate immune cell alterations and interactions in human squamous cell carcinomas and site-matched non-malignant, inflamed tissues. We found that a distinct population of intratumoral regulatory T cells (Tregs) received T cell receptor (TCR) signals from antigen-presenting cells and this Treg population was uniquely identified by co-expression of ICOS and IL-1 receptor type 1 (IL-1R1). Intratumoral IL-1R+ Tregs appeared activated and a TCR signal was sufficient to convert IL-1R1- Tregs to IL-1R1+ Tregs ex vivo. Overall, our work identifies an intratumoral Treg population that recognizes antigen in the tumor microenvironment and two biomarkers that allow for specific depletion of these Tregs. Finally, our approach also provides a blueprint for extricating tumor-unique therapeutic targets distinct from general inflammatory patterns in other tumors.
Yes there is potential Competing Interest. R.G. has received speaker fees from Illumina and Fluidigm and support from Juno Therapeutics and Janssen Pharma, has consulted for Takeda Vaccines, Juno Therapeutics and Infotech Soft, and has ownership interest in CellSpace Bio. E.G. declares ownership interest in Ozette Technologies. F.M, J.R.E and M.P. are holding the related patent “Specific Targeting of Tumor-infiltrating regulatory T cells (Tregs) using ICOS and IL-1R1” (US patent #63/092957).
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