Jing Ye, Benliang Wei, Guowei Zhou, Yantao Xu, Yi He, Xiheng Hu, Xiang Chen, Guanxiong Zhang, Hong Liu
{"title":"肿瘤微环境中细胞凋亡的多维特征及对黑色素瘤的治疗意义","authors":"Jing Ye, Benliang Wei, Guowei Zhou, Yantao Xu, Yi He, Xiheng Hu, Xiang Chen, Guanxiong Zhang, Hong Liu","doi":"10.1007/s13402-024-00930-0","DOIUrl":null,"url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Purpose</h3><p>Melanoma is widely utilized as a prominent model for the development of immunotherapy, thought an inadequate immune response can occur. Moreover, the development of apoptosis-related therapies and combinations with other therapeutic strategies is impeded by the limited understanding of apoptosis’s role within diverse tumor immune microenvironments (TMEs).</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>Here, we constructed an apoptosis-related tumor microenvironment signature (ATM) and employ multi-dimensional analysis to understand the roles of apoptosis in tumor microenvironment. We further assessed the clinical applications of ATM in nine independent cohorts, and anticipated the impact of ATM on cellular drug response in cultured cells.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Our ATM model exhibits robust performance in survival prediction in multiple melanoma cohorts. Different ATM groups exhibited distinct molecular signatures and biological processes. The low ATM group exhibited significant enrichment in B cell activation-related pathways. What’s more, plasma cells showed the lowest ATM score, highlighting their role as pivotal contributors in the ATM model. Mechanistically, the analysis of the interplay between plasma cells and other immune cells elucidated their crucial role in orchestrating an effective anti-tumor immune response. Significantly, the ATM signature exhibited associations with therapeutic efficacy of immune checkpoint blockade and the drug sensitivity of various agents, including FDA-approved and clinically utilized drugs targeting the VEGF signaling pathway. Finally, ATM was associated with tertiary lymphoid structures (TLS), exhibiting stronger patient stratification ability compared to classical “hot tumors”.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>Our findings indicate that ATM is a prognostic factor and is associated with the immune response and drug sensitivity in melanoma.</p>","PeriodicalId":9690,"journal":{"name":"Cellular Oncology","volume":null,"pages":null},"PeriodicalIF":6.6000,"publicationDate":"2024-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Multi-dimensional characterization of apoptosis in the tumor microenvironment and therapeutic relevance in melanoma\",\"authors\":\"Jing Ye, Benliang Wei, Guowei Zhou, Yantao Xu, Yi He, Xiheng Hu, Xiang Chen, Guanxiong Zhang, Hong Liu\",\"doi\":\"10.1007/s13402-024-00930-0\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<h3 data-test=\\\"abstract-sub-heading\\\">Purpose</h3><p>Melanoma is widely utilized as a prominent model for the development of immunotherapy, thought an inadequate immune response can occur. 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Multi-dimensional characterization of apoptosis in the tumor microenvironment and therapeutic relevance in melanoma
Purpose
Melanoma is widely utilized as a prominent model for the development of immunotherapy, thought an inadequate immune response can occur. Moreover, the development of apoptosis-related therapies and combinations with other therapeutic strategies is impeded by the limited understanding of apoptosis’s role within diverse tumor immune microenvironments (TMEs).
Methods
Here, we constructed an apoptosis-related tumor microenvironment signature (ATM) and employ multi-dimensional analysis to understand the roles of apoptosis in tumor microenvironment. We further assessed the clinical applications of ATM in nine independent cohorts, and anticipated the impact of ATM on cellular drug response in cultured cells.
Results
Our ATM model exhibits robust performance in survival prediction in multiple melanoma cohorts. Different ATM groups exhibited distinct molecular signatures and biological processes. The low ATM group exhibited significant enrichment in B cell activation-related pathways. What’s more, plasma cells showed the lowest ATM score, highlighting their role as pivotal contributors in the ATM model. Mechanistically, the analysis of the interplay between plasma cells and other immune cells elucidated their crucial role in orchestrating an effective anti-tumor immune response. Significantly, the ATM signature exhibited associations with therapeutic efficacy of immune checkpoint blockade and the drug sensitivity of various agents, including FDA-approved and clinically utilized drugs targeting the VEGF signaling pathway. Finally, ATM was associated with tertiary lymphoid structures (TLS), exhibiting stronger patient stratification ability compared to classical “hot tumors”.
Conclusion
Our findings indicate that ATM is a prognostic factor and is associated with the immune response and drug sensitivity in melanoma.
Cellular OncologyBiochemistry, Genetics and Molecular Biology-Cancer Research
CiteScore
10.40
自引率
1.50%
发文量
0
审稿时长
16 weeks
期刊介绍:
The Official Journal of the International Society for Cellular Oncology
Focuses on translational research
Addresses the conversion of cell biology to clinical applications
Cellular Oncology publishes scientific contributions from various biomedical and clinical disciplines involved in basic and translational cancer research on the cell and tissue level, technical and bioinformatics developments in this area, and clinical applications. This includes a variety of fields like genome technology, micro-arrays and other high-throughput techniques, genomic instability, SNP, DNA methylation, signaling pathways, DNA organization, (sub)microscopic imaging, proteomics, bioinformatics, functional effects of genomics, drug design and development, molecular diagnostics and targeted cancer therapies, genotype-phenotype interactions.
A major goal is to translate the latest developments in these fields from the research laboratory into routine patient management. To this end Cellular Oncology forms a platform of scientific information exchange between molecular biologists and geneticists, technical developers, pathologists, (medical) oncologists and other clinicians involved in the management of cancer patients.
In vitro studies are preferentially supported by validations in tumor tissue with clinicopathological associations.