New Insights Revealed About the Role of Mast Cells in Angiosarcoma Relating to Clinical Outcomes and Immuno-Oncology Pathways
Angiosarcoma, a rare and aggressive tumor of blood vessels, has been under intensive study due to its complex biology and poor prognosis. A groundbreaking study recently published in ‘Laboratory Investigation; a journal of technical methods and pathology’ has discovered a significant correlation between tumor-infiltrating mast cells and adverse clinical outcomes in angiosarcoma, bringing new urgency to research in mast cell-related immuno-oncology pathways.
DOI: 10.1016/j.labinv.2024.100323
The study led by Tai Sarah Beishan and colleagues from the Department of Nuclear Medicine and Molecular Imaging, Singapore General Hospital, and the Cancer Discovery Hub, National Cancer Centre Singapore, represents a significant advance in understanding the impacts of mast cells within angiosarcoma tumors. The team utilized both immunohistochemistry (H-scores) and NanoString transcriptomic profiling to quantify mast cell infiltration in a cohort of 60 angiosarcoma patients.
The H-scores showed a moderate but significant correlation with NanoString mast cell scores (r=0.525, p<0.001), substantiating the presence of mast cells in human angiosarcomas. Notably, these scores were positively correlated with head and neck tumor locations, non-epithelioid morphology, and lower tumor grades.
One of the most profound findings of the study was the relationship between mast cell enrichment and the regulation of key signaling pathways. NanoString mast cell scores positively correlated with pathways related to antigen presentation and were inversely associated with apoptosis, DNA damage repair, and cell proliferation, suggesting an interplay between mast cells and tumor behavior.
In the clinical context, the study’s outcomes are particularly alarming. Patients with mast cell-enriched angiosarcoma displayed markedly poorer progression-free survival, with a median of 0.2 years compared to 0.4 years and a hazard ratio (HR) of 3.05 (p=0.0489). There was also a noticeable trend towards worse overall survival in the mast cell-enriched group with a median of 0.2 years versus 0.6 years and an HR of 2.86 (p=0.0574).
Beishan and her colleagues’ findings provide the initial evidence of mast cells’ clinical and biological significance in angiosarcoma. The presence of mast cells may be indicative of immune evasion mechanisms within the tumor microenvironment, which could be contributing to the aggressive nature and poor outcome associated with this cancer type.
Despite the scope of these insights, this is only the first step. Further research will be required to delineate the precise roles that mast cells play in the biology of angiosarcoma. Understanding the mechanisms by which these immune cells influence tumor growth and patient prognosis could lead to the development of novel immunotherapeutic strategies against this lethal disease.
Researchers involved in the study include Elizabeth Chun Yong Lee, Boon Yee Lim, Bavani Kannan, Jing Yi Lee, Zexi Guo, Tun Kiat Ko, Cedric Chuan-Young Ng, and Bin Tean Teh from the National Cancer Centre Singapore, as well as Jason Yongsheng Chan from the Division of Medical Oncology, National Cancer Centre Singapore.
This study not only opens the door to expanding our knowledge of angiosarcoma but represents the potential for advancements in the treatment of various other cancer types where mast cells may play a similarly crucial role.
References
1. Tai, S. B., Lee, E. C. Y., Lim, B. Y., et al. (2024). Tumor-infiltrating Mast Cells in Angiosarcoma Correlate with Immuno-Oncology Pathways and Adverse Clinical Outcomes. Laboratory Investigation; a journal of technical methods and pathology, 100323. https://doi.org/10.1016/j.labinv.2024.100323
2. Agaugué, S., Carpentier, S., & Klatzmann, D. (2013). The Role of T Regulatory Cells and Toll-Like Receptors in the Pathogenesis of Human Inflammatory and Autoimmune Diseases. Immunity.
3. Galli, S. J., Borregaard, N., & Wynn, T. A. (2011). Phenotypic and Functional Plasticity of Cells of Innate Immunity: Macrophages, Mast Cells, and Neutrophils. Nature Immunology.
4. Coussens, L. M., Zitvogel, L., & Palucka, A. K. (2013). Neutralizing Tumor-Promoting Chronic Inflammation: A Magic Bullet? Science.
5. Brown, J. M., & Wilson, W. R. (2004). Exploiting Tumour Hypoxia in Cancer Treatment. Nature Reviews Cancer.
Keywords
1. Angiosarcoma Mast Cells
2. Immuno-Oncology Pathways
3. Tumor Microenvironment
4. Cancer Prognosis
5. Immunotherapy Strategies