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Multiomics surface receptor profiling of the NCI-60 tumor cell panel uncovers novel theranostics for cancer immunotherapy

BACKGROUND: Immunotherapy with immune checkpoint inhibitors (ICI) has revolutionized cancer therapy. However, therapeutic targeting of inhibitory T cell receptors such as PD-1 not only initiates a broad immune response against tumors, but also causes severe adverse effects. An ideal future stratifie...

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Autores principales: Heumos, Simon, Dehn, Sandra, Bräutigam, Konstantin, Codrea, Marius C., Schürch, Christian M., Lauer, Ulrich M., Nahnsen, Sven, Schindler, Michael
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9555072/
https://www.ncbi.nlm.nih.gov/pubmed/36221114
http://dx.doi.org/10.1186/s12935-022-02710-y
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author Heumos, Simon
Dehn, Sandra
Bräutigam, Konstantin
Codrea, Marius C.
Schürch, Christian M.
Lauer, Ulrich M.
Nahnsen, Sven
Schindler, Michael
author_facet Heumos, Simon
Dehn, Sandra
Bräutigam, Konstantin
Codrea, Marius C.
Schürch, Christian M.
Lauer, Ulrich M.
Nahnsen, Sven
Schindler, Michael
author_sort Heumos, Simon
collection PubMed
description BACKGROUND: Immunotherapy with immune checkpoint inhibitors (ICI) has revolutionized cancer therapy. However, therapeutic targeting of inhibitory T cell receptors such as PD-1 not only initiates a broad immune response against tumors, but also causes severe adverse effects. An ideal future stratified immunotherapy would interfere with cancer-specific cell surface receptors only. METHODS: To identify such candidates, we profiled the surface receptors of the NCI-60 tumor cell panel via flow cytometry. The resulting surface receptor expression data were integrated into proteomic and transcriptomic NCI-60 datasets applying a sophisticated multiomics multiple co-inertia analysis (MCIA). This allowed us to identify surface profiles for skin, brain, colon, kidney, and bone marrow derived cell lines and cancer entity-specific cell surface receptor biomarkers for colon and renal cancer. RESULTS: For colon cancer, identified biomarkers are CD15, CD104, CD324, CD326, CD49f, and for renal cancer, CD24, CD26, CD106 (VCAM1), EGFR, SSEA-3 (B3GALT5), SSEA-4 (TMCC1), TIM1 (HAVCR1), and TRA-1-60R (PODXL). Further data mining revealed that CD106 (VCAM1) in particular is a promising novel immunotherapeutic target for the treatment of renal cancer. CONCLUSION: Altogether, our innovative multiomics analysis of the NCI-60 panel represents a highly valuable resource for uncovering surface receptors that could be further exploited for diagnostic and therapeutic purposes in the context of cancer immunotherapy. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12935-022-02710-y.
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spelling pubmed-95550722022-10-13 Multiomics surface receptor profiling of the NCI-60 tumor cell panel uncovers novel theranostics for cancer immunotherapy Heumos, Simon Dehn, Sandra Bräutigam, Konstantin Codrea, Marius C. Schürch, Christian M. Lauer, Ulrich M. Nahnsen, Sven Schindler, Michael Cancer Cell Int Research BACKGROUND: Immunotherapy with immune checkpoint inhibitors (ICI) has revolutionized cancer therapy. However, therapeutic targeting of inhibitory T cell receptors such as PD-1 not only initiates a broad immune response against tumors, but also causes severe adverse effects. An ideal future stratified immunotherapy would interfere with cancer-specific cell surface receptors only. METHODS: To identify such candidates, we profiled the surface receptors of the NCI-60 tumor cell panel via flow cytometry. The resulting surface receptor expression data were integrated into proteomic and transcriptomic NCI-60 datasets applying a sophisticated multiomics multiple co-inertia analysis (MCIA). This allowed us to identify surface profiles for skin, brain, colon, kidney, and bone marrow derived cell lines and cancer entity-specific cell surface receptor biomarkers for colon and renal cancer. RESULTS: For colon cancer, identified biomarkers are CD15, CD104, CD324, CD326, CD49f, and for renal cancer, CD24, CD26, CD106 (VCAM1), EGFR, SSEA-3 (B3GALT5), SSEA-4 (TMCC1), TIM1 (HAVCR1), and TRA-1-60R (PODXL). Further data mining revealed that CD106 (VCAM1) in particular is a promising novel immunotherapeutic target for the treatment of renal cancer. CONCLUSION: Altogether, our innovative multiomics analysis of the NCI-60 panel represents a highly valuable resource for uncovering surface receptors that could be further exploited for diagnostic and therapeutic purposes in the context of cancer immunotherapy. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12935-022-02710-y. BioMed Central 2022-10-11 /pmc/articles/PMC9555072/ /pubmed/36221114 http://dx.doi.org/10.1186/s12935-022-02710-y Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Heumos, Simon
Dehn, Sandra
Bräutigam, Konstantin
Codrea, Marius C.
Schürch, Christian M.
Lauer, Ulrich M.
Nahnsen, Sven
Schindler, Michael
Multiomics surface receptor profiling of the NCI-60 tumor cell panel uncovers novel theranostics for cancer immunotherapy
title Multiomics surface receptor profiling of the NCI-60 tumor cell panel uncovers novel theranostics for cancer immunotherapy
title_full Multiomics surface receptor profiling of the NCI-60 tumor cell panel uncovers novel theranostics for cancer immunotherapy
title_fullStr Multiomics surface receptor profiling of the NCI-60 tumor cell panel uncovers novel theranostics for cancer immunotherapy
title_full_unstemmed Multiomics surface receptor profiling of the NCI-60 tumor cell panel uncovers novel theranostics for cancer immunotherapy
title_short Multiomics surface receptor profiling of the NCI-60 tumor cell panel uncovers novel theranostics for cancer immunotherapy
title_sort multiomics surface receptor profiling of the nci-60 tumor cell panel uncovers novel theranostics for cancer immunotherapy
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9555072/
https://www.ncbi.nlm.nih.gov/pubmed/36221114
http://dx.doi.org/10.1186/s12935-022-02710-y
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