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Phosphoinositide 3-kinase/Akt and its related signaling pathways in the regulation of tumor-associated macrophages polarization

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Abstract

Tumor-associated macrophages (TAMs) are a type of functionally plastic immune cell population in tumor microenvironment (TME) and mainly polarized into two phenotypes: M2 and M1-like TAMs. The M2-like TAMs could stimulate tumor growth and metastasis, tissue remodeling and immune-suppression, whereas M1-like TAMs could initiate immune response to dampen tumor progression. TAMs with different polarization phenotypes can produce various kinds of cytokines, chemokines and growth factors to regulate immunity and inflammatory responses. It is an effective method to treat cancer through ameliorating TME and modulating TAMs by converting M2 into M1-like phenotype. However, intracellular signaling mechanisms underlying TAMs polarization are largely undefined. Phosphoinositide 3-kinase (PI3K)/Akt is an important signaling pathway participating in M2-like TAMs polarization, survival, growth, proliferation, differentiation, apoptosis and cytoskeleton rearrangement. In the present review, we analyzed the mechanism of TAMs polarization focusing on PI3K/Akt and its downstream mitogen‑activated protein kinase (MAPK) as well as nuclear factor kappa B (NF-κB) signaling pathways, thus provides the first evidence of intracellular targets for cancer immunotherapy.

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Fig. 1

Adapted from reference [10]

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Adapted from reference [54]

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The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.

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Author notes

  1. Depeng Yang, Lijun Yang and Jialing Cai have contributed equally to this manuscript.

Authors and Affiliations

  1. School of Life Sciences and Technology, Harbin Institute of Technology, Harbin, 150001, Heilongjiang, China

    Depeng Yang, Lijun Yang, Jialing Cai & Huaxin Li

  2. Institute of Basic and Translational Medicine, Shaanxi Key Laboratory of Ischemic Cardiovascular Disease, Shaanxi Key Laboratory of Brain Disorders, Xi’an Medical University, Xi’an, 710021, Shaanxi, China

    Ying Hou

  3. Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, School of Biological Science and Medical Engineering, Beijing Advanced Innovation Centre for Biomedical Engineering, Beihang University, Beijing, 100191, China

    Zheng Xing

Authors
  1. Depeng Yang
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  2. Lijun Yang
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  3. Jialing Cai
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  4. Huaxin Li
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  5. Zheng Xing
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  6. Ying Hou
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Contributions

All authors contributed to the study conception and design. DY, LY and JC contributed equally to this work. DY and LY wrote the paper. JC made the pictures. HL and ZX made the tables. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Ying Hou.

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Yang, D., Yang, L., Cai, J. et al. Phosphoinositide 3-kinase/Akt and its related signaling pathways in the regulation of tumor-associated macrophages polarization. Mol Cell Biochem 477, 2469–2480 (2022). https://doi.org/10.1007/s11010-022-04461-w

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