CCL4 Signaling in the Tumor Microenvironment

  • Naofumi MukaidaEmail author
  • So-ichiro Sasaki
  • Tomohisa Baba
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1231)


CCL4, a CC chemokine, previously known as macrophage inflammatory protein (MIP)-1β, has diverse effects on various types of immune and nonimmune cells by the virtue of its interaction with its specific receptor, CCR5, in collaboration with related but distinct CC chemokines such as CCL3 and CCL5, which can also bind CCR5. Several lines of evidence indicate that CCL4 can promote tumor development and progression by recruiting regulatory T cells and pro-tumorigenic macrophages, and acting on other resident cells present in the tumor microenvironment, such as fibroblasts and endothelial cells, to facilitate their pro-tumorigenic capacities. These observations suggest the potential efficacy of CCR5 antagonists for cancer treatment. On the contrary, under some situations, CCL4 can enhance tumor immunity by recruiting cytolytic lymphocytes and macrophages with phagocytic ability. Thus, presently, the clinical application of CCR5 antagonists warrants more detailed analysis of the role of CCL4 and other CCR5-binding chemokines in the tumor microenvironment.


Arrestin CCR5 Chemokine Chemotaxis Cytolytic lymphocyte Endothelial cell Fibroblast Macrophage inflammatory protein Trimeric G protein Human immunodeficiency virus Macrophage Metastasis Myeloid suppressor cells Neutrophils Regulatory T cell 



This work was supported partly by the Grant-in-Aid for Scientific Research (C) from the Japan Society for the Promotion of Science (JSPS) KAKEHI grant number 17K07159.


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Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  • Naofumi Mukaida
    • 1
    Email author
  • So-ichiro Sasaki
    • 1
  • Tomohisa Baba
    • 1
  1. 1.Division of Molecular Bioregulation, Cancer Research InstituteKanazawa UniversityKanazawaJapan

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