TABLE 2.
Summary of studies evaluating the role of TAMs in HCC therapy.
| Study (Year) | Product | Mechanism of action | Study subjects | Result |
|---|---|---|---|---|
| Li CW. et al. (2018) | nanoliposome-loaded C6-ceramide (LipC6) | Depletion of TAMs | CCl4 and TAg-transformed B6/WT-19 HCC cell line orthotopic mouse model | In HCC mice, administration of LipC6 reduced TAMs population and reduced their production of ROS as well as its ability to inhibit antitumor immune response |
| Xie et al. (2023) | Clodronate liposomes | Depletion of TAMs | PLC/PRF/5, MHCC97H, H22 and Hepa1-6 HCC cell line orthotopic mouse models | Suppressed tumor growth and metastasis |
| Zhang P. et al. (2022) | Doxorubicin-liposome and clodronate-liposome | Depletion of TAMs | diethylnitrosamine (DEN) induced primary HCC rat model | Depletion of macrophages by clodronate-liposome, in combination with Doxorubicin-liposome, significantly inhibited HCC progression compared with the use of Doxorubicin-liposome alone |
| Zhou et al. (2017) | Sorafenib and TACE | Termination of macrophages recruitment | Walker-256 HCC cell line xenograft and orthotopic rat models | Inhibition of tumor growth and angiogenesis |
| Teng et al. (2017) | CCR2 monoclonal antibody | Termination of macrophages recruitment | miR-122-knockout HCC mouse mode | Inhibition of tumor growth and activation of natural killer cells |
| Li et al. (2017) | CCR2 antagonist | Termination of macrophages recruitment | Hepa1-6 and LPC-H12 HCC cell line xenograft and Hepa1-6 orthotopic mouse models | Suppressed tumor growth and metastasis and reduced recurrence. Improved survival and activation of CD8⁺ T cells |
| Chen et al. (2022) | HMGA1 siRNA | Termination of macrophages recruitment | HepG2, Huh7, Hep3B, SNU-423, HCC-LM3, MHC C-97H, SK-Hep1, and SMMC-7721 HCC cell lines and SNU-423 orthotopic xenograft mouse models | Inhibition of HMGA1 expression reduced TAMs infiltration and Enhanced immunotherapy efficacy of CCL2-CCR2 signaling in HCC |
| Chen et al. (2014) | Sorafenib and CXCR4 antagonist (AMD3100) | Termination of macrophages recruitment | HCA-1 HCC cell line orthotopic mouse model | Blocking SDF-1α/CXCR4 reduced hypoxia-mediated HCC desmoplasia and increased the efficacy of sorafenib treatment |
| Chen et al. (2015) | CXCR4 antagonist | Termination of macrophages recruitment | HCA-1, JHH-7 or Hep3B HCC cell line orthotopic mouse models | Relieved regional immunosuppression and promoted anti-PD-1 treatment in a sorafenib-resistance HCC model |
| Ao et al. (2017) | CSF-1 receptor antagonist | Reprogramming polarization of TAMs | Hepa1-6, HepG2, or HCCLM3 HCC cell line orthotopic mouse models | Suppressed tumor growth and increased the activity of CD8⁺ T cells |
| Xu F. et al. (2020) | Listeria-based HCC vaccine (Lmdd-MPF) | Reprogramming polarization of TAMs | Hepa1–6/MPFG HCC cell line xenograft mouse model and clinical tissue samples collected from HCC patients | Restored the T-cell reactivity to the anti-PD-1 blockade |
| Wu et al. (2019a) | TREM-1 inhibitor (GF9) | Reprogramming polarization of TAMs | Hepa1–6 HCC cell line orthotopic mouse model and clinical tissue samples collected from HCC patients | Blocking TREM-1 with GF9 inhibitor reversed immunosuppression and anti-PD-L1 resistance in HCC |
| Yang et al. (2012) | 17β-estradiol (E2) | Reprogramming polarization of TAMs | ANA-1 cells, Hepa1-6 HCC cell line and Heps HCC cell line xenograft and orthotopic mouse models | E2 inhibits alternative activation of macrophages and HCC progression by keeping ERβ away from interacting with ATP5J, thus suppressing the JAK1-STAT6 signaling pathway |
| Rodell et al. (2018) | TLR7/8-agonist-loaded nanoparticles | Reprograming polarization of TAMs | RAW 264.7 cell line, Murine bone marrow-derived macrophages (BMDMs) and xenograft mouse models | Promoted reprogramming of the TAMs and antitumor immunity |
| Wang X. et al. (2021) | CCL2 and CCL5 antibody (BisCCL2/5i) | Reprograming polarization of TAMs | clinical tissue samples collected from HCC patients, Hepa1–6 HCC cell line and orthotopic mouse models | The combination of BisCCL2/5i with anti-PD-L1 reduced immunosuppression in the TME and achieved long-term survival in mouse HCC models |
| Chang et al. (2020) | NanoMnSor to co-deliver sorafenib and MnO2 | Reprograming polarization of TAMs | HCA-1, JHH-7 and Hep3B HCC cell lines and HCA-1 orthotopic mouse models | Reprogrammed tumor-promoting macrophages transition to immunostimulatory M1 macrophages, increased CD8⁺ cytotoxic T cells in tumors, and enhanced the efficacy of the PD-L1 antibody |
| Liu et al. (2020) | Selenium nanoparticles (SeNPs) | Reprograming polarization of TAMs | HepG2 HCC cell line | Promoting M2 to M1 macrophages and increasing the infiltration of natural killer cells into tumors |
TAMs, tumor-associated macrophages; HCC, hepatocellular carcinoma; CCl4, carbon tetrachloride; ROS, reactive oxygen species; TACE, transcatheter arterial chemoembolization; CCR2, chemokine (C-C motif) receptor 2; HMGA1, high mobility group A1; CCL2, chemokine (C-C motif) ligand 2; CXCR4, chemokine (C-X-C motif) receptor 4; SDF-1α (CXCL12), chemokine (C-X-C motif) ligand 12; CSF-1, macrophage colony stimulating factor-1; TREM-1, triggering receptor expressed on myeloid cells-1; E2, estradiol; ERβ, estrogen receptor β; ATP5J, ATP synthase-coupling factor 6; JAK1, janus kinase 1; STAT6, signal transducer and activator of transcription 6; TLR7/8, toll-like receptor7/8; CCL5, chemokine (C-C motif) ligand 5; TME, tumor microenvironment; PD-1, programmed cell death protein 1; PD-L1, programmed cell death-ligand 1.