Journal
FRONTIERS IN IMMUNOLOGY
Volume 12, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2021.741305
Keywords
tumor hypoxia; hypoxic tumor microenvironment; tumor-associated macrophages; macrophage polarization; macrophage functional transformation
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Funding
- National Natural Science Foundation of China [81871323, 81801665, 81901709]
- Natural Science Foundation of Guangdong Province [2018B030311024, 2019A1515011918]
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TAMs are crucial immune cells in tumors, and their functional transformation from M1 to M2 as tumors progress plays a key role in immunosuppression and tumor promotion processes. Understanding the mechanism of TAM functional transformation in the hypoxic environment is essential for developing novel tumor immunotherapeutic strategies.
Tumor-associated macrophages (TAMs) are some of the most abundant immune cells within tumors and perform a broad repertoire of functions via diverse phenotypes. On the basis of their functional differences in tumor growth, TAMs are usually categorized into two subsets of M1 and M2. It is well established that the tumor microenvironment (TME) is characterized by hypoxia along with tumor progression. TAMs adopt an M1-like pro-inflammatory phenotype at the early phases of oncogenesis and mediate immune response that inhibits tumor growth. As tumors progress, anabatic hypoxia of the TME gradually induces the M2-like functional transformation of TAMs by means of direct effects, metabolic influence, lactic acidosis, angiogenesis, remodeled stroma, and then urges them to participate in immunosuppression, angiogenesis and other tumor-supporting procedure. Therefore, thorough comprehension of internal mechanism of this TAM functional transformation in the hypoxic TME is of the essence, and might provide some novel insights in hypoxic tumor immunotherapeutic strategies.
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