TMIC-33. ARGINASE-1 AND ITS ROLE IN THE GLIOBLASTOMA MICROENVIRONMENTстатья из журнала
Аннотация: Abstract An average GBM has roughly 30% infiltration of myeloid cells, the highest reported case at 70% infiltration, with some variation dependent on subtype. When we consider this fact in combination with the advent and success of immunotherapies in similar cancer types, the logical next step follows that myeloid cells, which are of the immune lineage, have the potential to clear this aberrant growth. Known for their incredible phagocytic capacity, myeloid cells are among the first responders to an injury to control pathogens and clear apoptotic cells from the site of an insult. Myeloid cells, through poorly understood mechanisms, undergo a switch after 3-5 days from attacking pathogens and clearing dead cells to secretion of growth cytokines to promote wound healing. We posit these myeloid cells may be tricked into erroneously supporting the tumor cells in an attempt to “heal the wound” instead of mounting an immune response. The enzyme responsible for this switch from pathogen response to wound healing is called Arginase-1 (Arg1). When Arg1 is upregulated it has a two pronged effect, the first is creation of peroxynitrite which is actively immunosuppressive to both myeloid and T-cells. The second is an increase in ornithine when Arg1 cleaves arginine into ornithine and urea, which can be used to create the building blocks for cellular growth as well as to create collagen, which is necessary for wound repair and found in high levels in brain tumors. Our hypothesis is that through manipulation of the Arg1 axis in myeloid cells we will increase anti-tumor response. We show the groundwork for evaluating whether or not this is a viable therapeutic target in GBM as well as assess currently available compounds for inhibition or Arg1 in the CNS.
Год издания: 2022
Авторы: Daniel B. Zamler, Takashi Shingu, Shan Jiang, F. Richard Yu, Yingda Jiang, Giulio Draetta, Jian Hu
Издательство: Oxford University Press
Источник: Neuro-Oncology
Ключевые слова: Cancer Research and Treatments, Immune cells in cancer, Nanoplatforms for cancer theranostics
Другие ссылки: Neuro-Oncology (PDF)
Neuro-Oncology (HTML)
PubMed Central (HTML)
Neuro-Oncology (HTML)
PubMed Central (HTML)
Открытый доступ: bronze
Том: 24
Выпуск: Supplement_7
Страницы: vii278–vii278