M1-like macrophages change tumor blood vessels and microenvironment in murine melanoma

Autor: Natalia Kamińska, Jolanta Pamuła-Piłat, Ryszard Smolarczyk, Stanisław Szala, Justyna Czapla, Daria Skwarzyńska, Magdalena Jarosz-Biej, Klaudia Kulik, Sybilla Matuszczak, Tomasz Cichoń
Jazyk: angličtina
Rok vydání: 2018
Předmět:
0301 basic medicine
CD4-Positive T-Lymphocytes
Angiogenesis
Cancer Treatment
Melanoma
Experimental
lcsh:Medicine
Angiogenesis Inhibitors
NK cells
CD8-Positive T-Lymphocytes
Neovascularization
White Blood Cells
Mice
0302 clinical medicine
Animal Cells
Medicine and Health Sciences
Tumor Cells
Cultured
Tumor Microenvironment
Vaccines
DNA
Medicine
Lymphocytes
skin and connective tissue diseases
lcsh:Science
Vaccines
Multidisciplinary
Antibiotics
Antineoplastic
Neovascularization
Pathologic
T Cells
Melanoma
Interleukin-12
Killer Cells
Natural
Infectious Diseases
Oncology
Interleukin 12
Female
medicine.symptom
Cellular Types
Anatomy
Research Article
Infectious Disease Control
Immune Cells
Immunology
Cytotoxic T cells
03 medical and health sciences
Immune system
Animals
Cell Proliferation
Tumor microenvironment
Blood Cells
business.industry
Macrophages
lcsh:R
Biology and Life Sciences
Cell Biology
Endoglin
medicine.disease
Mice
Inbred C57BL
030104 developmental biology
Tumor progression
Doxorubicin
Cancer research
Cardiovascular Anatomy
Blood Vessels
lcsh:Q
business
030215 immunology
Zdroj: PLoS ONE, Vol 13, Iss 1, p e0191012 (2018)
PLoS ONE
ISSN: 1932-6203
Popis: Tumor-associated macrophages (TAMs) play a significant role in at least two key processes underlying neoplastic progression: angiogenesis and immune surveillance. TAMs phenotypic changes play important role in tumor vessel abnormalization/ normalization. M2-like TAMs stimulate immunosuppression and formation of defective tumor blood vessels leading to tumor progression. In contrast M1-like TAMs trigger immune response and normalize irregular tumor vascular network which should sensitize cancer cells to chemo- and radiotherapy and lead to tumor growth regression. Here, we demonstrated that combination of endoglin-based DNA vaccine with interleukin 12 repolarizes TAMs from tumor growth-promoting M2-like phenotype to tumor growth-inhibiting M1-like phenotype. Combined therapy enhances tumor infiltration by CD4+, CD8+ lymphocytes and NK cells. Depletion of TAMs as well as CD8+ lymphocytes and NK cells, but not CD4+ lymphocytes, reduces the effect of combined therapy. Furthermore, combined therapy improves tumor vessel maturation, perfusion and reduces hypoxia. It caused that suboptimal doses of doxorubicin reduced the growth of tumors in mice treated with combined therapy. To summarize, combination of antiangiogenic drug and immunostimulatory agent repolarizes TAMs phenotype from M2-like (pro-tumor) into M1-like (anti-tumor) which affects the structure of tumor blood vessels, improves the effect of chemotherapy and leads to tumor growth regression.
Databáze: OpenAIRE
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