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Sevoflurane depletes macrophages from the melanoma microenvironment
- Source :
- PLoS ONE, Vol 15, Iss 5, p e0233789 (2020), PLoS ONE
- Publication Year :
- 2020
- Publisher :
- Public Library of Science (PLoS), 2020.
-
Abstract
- Background With more than 18 million annual new cases, cancer belongs to the major challenges of modern healthcare. Surgical resection of solid tumours under general anaesthesia is the prime therapy. Different aspects of anaesthesia are under discussion to independently influence the long-term outcome of cancer patients. Most recently, the commonly used volatile anaesthetics like sevoflurane have entered the spotlight, as retrospective studies suggest a detrimental outcome in certain cancer aetiologies with sparse mechanistic understanding. Our objective was to investigate this concept in a murine melanoma model, herein comparing the consequence of inhalative and injection anesthesia on tumour composition and growth. Methods We used a murine model of malignant melanoma in male, adult C57BL/6 mice (n = 92), induced by the subcutaneous injection of B16-F10 cells. We either exposed the melanoma cells to sevoflurane before implantation or subjected the animals to single or double anaesthesia with either volatile or injection drugs. After a maximum follow-up of 4 weeks, leucocytes within the tumour microenvironment (TME) were comprehensively analysed by flow cytometry with focus on tumor-associated macrophages (TAM). Results We found that exposure of melanoma cells to sevoflurane before implantation induced long-lasting transcriptome changes and aggravated tumour growth, without extensive changes of the TME. Contrastingly, both a single and double anaesthesia with sevoflurane led to a significant reduction of TAMs (injection vs. sevoflurane: 2,0 vs. 0.3% and 1.2 vs. 0.6%, respectively), whilst increasing PD-L1 expression on the remaining cells (mean fluorescent intensity injection vs. sevoflurane: 3,804 vs. 7,143 and 9,090 vs. 32,228, respectively). No changes in tumour growth were observed in these groups. Conclusion In sharp contrast to the detrimental impact of sevoflurane on patients' outcome reported in retrospective clinical studies, we propose here that sevoflurane might actually exert a beneficial effect by decreasing TAMs within the TME, rendering the tumour again susceptible for cytotoxic T cells and immunotherapies. Further research is warranted to delineate, how these results translate into the clinic.
- Subjects :
- Melanomas
Male
0301 basic medicine
Oncology
Skin Neoplasms
Melanoma, Experimental
Monocytes
Transcriptome
White Blood Cells
Mice
Subcutaneous injection
0302 clinical medicine
Anesthesiology
Animal Cells
030202 anesthesiology
Medicine and Health Sciences
Tumor Microenvironment
Cytotoxic T cell
Anesthesia
General anaesthesia
Melanoma
Cultured Tumor Cells
Multidisciplinary
medicine.diagnostic_test
Pharmaceutics
Anesthetics, Inhalation
Melanoma Cells
Medicine
Biological Cultures
Cellular Types
Research Article
medicine.drug
medicine.medical_specialty
Immune Cells
Science
Immunology
Research and Analysis Methods
Sevoflurane
Flow cytometry
03 medical and health sciences
Drug Therapy
Internal medicine
medicine
Animals
Molecular Biology Techniques
Molecular Biology
Blood Cells
Euthanasia
business.industry
Macrophages
Biology and Life Sciences
Cancers and Neoplasms
Cancer
Cell Biology
Cell Cultures
medicine.disease
Mice, Inbred C57BL
030104 developmental biology
business
Cloning
Subjects
Details
- ISSN :
- 19326203
- Volume :
- 15
- Database :
- OpenAIRE
- Journal :
- PLOS ONE
- Accession number :
- edsair.doi.dedup.....8d55ef7c56afe2debceaed2b5dc9a03a