Review Article

Preclinical and Clinical Therapeutic Strategies Affecting Tumor-Associated Macrophages in Hepatocellular Carcinoma

Table 2

Preclinical TAM-targeted therapies in HCC.

AuthorProductMechanism of actionAnimal modelResults

Wang et al. [52]Clodronate-liposomesDepletion of TAMsHepa1-6 HCC cell line xenograft and orthotopic mouse modelInhibition of tumor growth
Zhang et al. [65]Sorafenib and zoledronic acid or clodronate-liposomesDepletion of TAMsHCCLM3-R and SMMC7721 HCC cell line xenograft mouse modelsInhibition of tumor growth, lung metastasis, and angiogenesis
Li et al. [55]CCR2 antagonistInhibiting recruitment of monocytes
M2 polarization of TAMs
Hepa1-6 and LPC-H12 HCC cell line xenograft and Hepa1-6 orthotopic mouse modelInhibition of tumor growth and metastasis, reduction of recurrence, enhanced survival, and activation of CD8+ T cells
Yao et al. [56]CCR2 antagonistInhibiting recruitment of monocytesHepa1-6 or LPC-H12 HCC cell line xenograft and Hepa1-6 orthotopic mouse modelsInhibition of tumor growth, increase in CD8+ T cells, and potentiation effect of sorafenib
Teng et al. [57]CCR2 monoclonal antibodyInhibiting recruitment of monocytesmiR-122-knockout HCC mouse modelInhibition of tumor growth and activation of natural killer cells
Zhou et al. [68]Sorafenib and TACEInhibiting recruitment of monocytesWalker-256 HCC cell line xenograft and orthotopic rat modelsInhibition of tumor growth and angiogenesis
Tan et al. [58]BaicalinReprogramming polarization of TAMsMHCC97L HCC cell line orthotopic mouse modelInhibition of tumor growth
Ao et al. [59]CSF-1 receptor antagonistReprogramming polarization of TAMsHepa1-6, HepG2, or HCCLM3 HCC cell line orthotopic mouse modelDelayed tumor growth and increase in CD8+ T cells
Sprinzl et al. [62]SorafenibReprogramming polarization of TAMsHepatitis B virus replicating HBV1.3.32 or albumin-promoter-controlled lymphotoxin-a/b transgenic miceActivation of natural killer cells and cytotoxicity
Wan et al. [60]IL-6 receptor monoclonal antibodyBlocking downstream effect of TAM productsHepG2 or human HCC cell line xenograft mouse modelReduction of tumor growth