Leveraging Single-Cell Multi-Omics to Decode Tumor Microenvironment Diversity and Therapeutic Resistance
Recent developments in single-cell multi-omics technologies have provided the ability to identify diverse cell types and decipher key components of the tumor microenvironment (TME), leading to important advancements toward a much deeper understanding of how tumor microenvironment heterogeneity contr...
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MDPI AG
2025-01-01
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| author | Hussein Sabit Borros Arneth Timothy M. Pawlik Shaimaa Abdel-Ghany Aysha Ghazy Rawan M. Abdelazeem Amany Alqosaibi Ibtesam S. Al-Dhuayan Jawaher Almulhim Noof A. Alrabiah Ahmed Hashash |
| author_facet | Hussein Sabit Borros Arneth Timothy M. Pawlik Shaimaa Abdel-Ghany Aysha Ghazy Rawan M. Abdelazeem Amany Alqosaibi Ibtesam S. Al-Dhuayan Jawaher Almulhim Noof A. Alrabiah Ahmed Hashash |
| author_sort | Hussein Sabit |
| collection | DOAJ |
| description | Recent developments in single-cell multi-omics technologies have provided the ability to identify diverse cell types and decipher key components of the tumor microenvironment (TME), leading to important advancements toward a much deeper understanding of how tumor microenvironment heterogeneity contributes to cancer progression and therapeutic resistance. These technologies are able to integrate data from molecular genomic, transcriptomic, proteomics, and metabolomics studies of cells at a single-cell resolution scale that give rise to the full cellular and molecular complexity in the TME. Understanding the complex and sometimes reciprocal relationships among cancer cells, CAFs, immune cells, and ECs has led to novel insights into their immense heterogeneity in functions, which can have important consequences on tumor behavior. In-depth studies have uncovered immune evasion mechanisms, including the exhaustion of T cells and metabolic reprogramming in response to hypoxia from cancer cells. Single-cell multi-omics also revealed resistance mechanisms, such as stromal cell-secreted factors and physical barriers in the extracellular matrix. Future studies examining specific metabolic pathways and targeting approaches to reduce the heterogeneity in the TME will likely lead to better outcomes with immunotherapies, drug delivery, etc., for cancer treatments. Future studies will incorporate multi-omics data, spatial relationships in tumor micro-environments, and their translation into personalized cancer therapies. This review emphasizes how single-cell multi-omics can provide insights into the cellular and molecular heterogeneity of the TME, revealing immune evasion mechanisms, metabolic reprogramming, and stromal cell influences. These insights aim to guide the development of personalized and targeted cancer therapies, highlighting the role of TME diversity in shaping tumor behavior and treatment outcomes. |
| format | Article |
| id | doaj-art-b7b1a6fe408f4a8bbc23a56720e2359f |
| institution | Kabale University |
| issn | 1424-8247 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj-art-b7b1a6fe408f4a8bbc23a56720e2359f2025-01-24T13:45:17ZengMDPI AGPharmaceuticals1424-82472025-01-011817510.3390/ph18010075Leveraging Single-Cell Multi-Omics to Decode Tumor Microenvironment Diversity and Therapeutic ResistanceHussein Sabit0Borros Arneth1Timothy M. Pawlik2Shaimaa Abdel-Ghany3Aysha Ghazy4Rawan M. Abdelazeem5Amany Alqosaibi6Ibtesam S. Al-Dhuayan7Jawaher Almulhim8Noof A. Alrabiah9Ahmed Hashash10Department of Medical Biotechnology, College of Biotechnology, Misr University for Science and Technology, P.O. Box 77, Giza 3237101, EgyptInstitute of Laboratory Medicine and Pathobiochemistry, Molecular Diagnostics, Hospital of the Universities of Giessen and Marburg (UKGM), Philipps University Marburg, Baldingerstr. 1, 35043 Marburg, GermanyDepartment of Surgery, The Ohio State University, Wexner Medical Center, Columbus, OH 43210, USADepartment of Environmental Biotechnology, College of Biotechnology, Misr University for Science and Technology, P.O. Box 77, Giza 3237101, EgyptDepartment of Agricultural Biotechnology, College of Biotechnology, Misr University for Science and Technology, P.O. Box 77, Giza 3237101, EgyptDepartment of Medical Biotechnology, College of Biotechnology, Misr University for Science and Technology, P.O. Box 77, Giza 3237101, EgyptDepartment of Biology, College of Science, Imam Abdulrahman bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi ArabiaDepartment of Biology, College of Science, Imam Abdulrahman bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi ArabiaDepartment of Biological Sciences, King Faisal University, Alahsa 31982, Saudi ArabiaDepartment of Biological Sciences, King Faisal University, Alahsa 31982, Saudi ArabiaDepartment of Biomedicine, Texas A&M University, College Station, TX 77843, USARecent developments in single-cell multi-omics technologies have provided the ability to identify diverse cell types and decipher key components of the tumor microenvironment (TME), leading to important advancements toward a much deeper understanding of how tumor microenvironment heterogeneity contributes to cancer progression and therapeutic resistance. These technologies are able to integrate data from molecular genomic, transcriptomic, proteomics, and metabolomics studies of cells at a single-cell resolution scale that give rise to the full cellular and molecular complexity in the TME. Understanding the complex and sometimes reciprocal relationships among cancer cells, CAFs, immune cells, and ECs has led to novel insights into their immense heterogeneity in functions, which can have important consequences on tumor behavior. In-depth studies have uncovered immune evasion mechanisms, including the exhaustion of T cells and metabolic reprogramming in response to hypoxia from cancer cells. Single-cell multi-omics also revealed resistance mechanisms, such as stromal cell-secreted factors and physical barriers in the extracellular matrix. Future studies examining specific metabolic pathways and targeting approaches to reduce the heterogeneity in the TME will likely lead to better outcomes with immunotherapies, drug delivery, etc., for cancer treatments. Future studies will incorporate multi-omics data, spatial relationships in tumor micro-environments, and their translation into personalized cancer therapies. This review emphasizes how single-cell multi-omics can provide insights into the cellular and molecular heterogeneity of the TME, revealing immune evasion mechanisms, metabolic reprogramming, and stromal cell influences. These insights aim to guide the development of personalized and targeted cancer therapies, highlighting the role of TME diversity in shaping tumor behavior and treatment outcomes.https://www.mdpi.com/1424-8247/18/1/75single-cell multi-omicstumor microenvironment (TME)cancer therapeutic resistanceimmune evasionmetabolic reprogrammingpersonalized cancer therapy |
| spellingShingle | Hussein Sabit Borros Arneth Timothy M. Pawlik Shaimaa Abdel-Ghany Aysha Ghazy Rawan M. Abdelazeem Amany Alqosaibi Ibtesam S. Al-Dhuayan Jawaher Almulhim Noof A. Alrabiah Ahmed Hashash Leveraging Single-Cell Multi-Omics to Decode Tumor Microenvironment Diversity and Therapeutic Resistance Pharmaceuticals single-cell multi-omics tumor microenvironment (TME) cancer therapeutic resistance immune evasion metabolic reprogramming personalized cancer therapy |
| title | Leveraging Single-Cell Multi-Omics to Decode Tumor Microenvironment Diversity and Therapeutic Resistance |
| title_full | Leveraging Single-Cell Multi-Omics to Decode Tumor Microenvironment Diversity and Therapeutic Resistance |
| title_fullStr | Leveraging Single-Cell Multi-Omics to Decode Tumor Microenvironment Diversity and Therapeutic Resistance |
| title_full_unstemmed | Leveraging Single-Cell Multi-Omics to Decode Tumor Microenvironment Diversity and Therapeutic Resistance |
| title_short | Leveraging Single-Cell Multi-Omics to Decode Tumor Microenvironment Diversity and Therapeutic Resistance |
| title_sort | leveraging single cell multi omics to decode tumor microenvironment diversity and therapeutic resistance |
| topic | single-cell multi-omics tumor microenvironment (TME) cancer therapeutic resistance immune evasion metabolic reprogramming personalized cancer therapy |
| url | https://www.mdpi.com/1424-8247/18/1/75 |
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