Targeting tumor-associated macrophages in hepatocellular carcinoma: biology, strategy, and immunotherapy

Abstract

Hepatocellular carcinoma (HCC), one of the most malignant tumors, is characterized by its stubborn immunosuppressive microenvironment. As one of the main members of the tumor microenvironment (TME) of HCC, tumor-associated macrophages (TAMs) play a critical role in its occurrence and development, including stimulating angiogenesis, enhancing immunosuppression, and promoting the drug resistance and cancer metastasis. This review describes the origin as well as phenotypic heterogeneity of TAMs and their potential effects on the occurrence and development of HCC and also discusses about various adjuvant therapy based strategies that can be used for targeting TAMs. In addition, we have highlighted different treatment modalities for TAMs based on immunotherapy, including small molecular inhibitors, immune checkpoint inhibitors, antibodies, tumor vaccines, adoptive cellular immunotherapy, and nanocarriers for drug delivery, to explore novel combination therapies and provide feasible therapeutic options for clinically improving the prognosis and quality of life of HCC patients.

The application of a self-designed microfluidic lung chip in the assessment of different inhalable aerosols

“…This regulation is inuenced by factors such as the type of cell, the type of stimulus, and its intensity. 28 IL-8 (CXCL8) is a cytokine that promotes inammation and is essential for the response of the immune system to infection and inammation. 29,30 Earlier studies suggest that exposure to various aerosols stimulates the production of IL-8, leading to exacerbated inammatory responses that negatively impact lung function and overall health.…”

The role of tumor‐associated macrophages in hepatocellular carcinoma progression: A narrative review

“…We have demonstrated the influence of several major signaling pathways and multiple substances in the tumor microenvironment in the oncogenesis of TAMs, and at the same time, we have discussed the combination of multiple HCC therapies through modulating TAMs, which effectively mitigates drug resistance and enhances curative efficacy, with the promise of improved prognosis and better survival. There have been several reviews talking about origin, pathogenesis, or therapeutic strategies between TAM and HCC, 151–155 and this paper both completes some parts of them and detailing the crosstalk between TAM and HCC from a different perspective. This article complements them by making the relationship between TAM and HCC clearer, providing a more complete understanding of TAM and HCC, and offering valuable information for the future discovery of effective strategies for targeting TAM for the treatment of HCC.…”

PEG‐Sheddable Nanodrug Remodels Tumor Microenvironment to Promote Effector T Cell Infiltration and Revise Their Exhaustion for Breast Cancer Immunotherapy

“…However, T cells and M2-like macrophages throughout the body can also be affected by therapeutic agents, leading to systematic immune-related adverse events (irAEs). [27][28][29] Owing to the incomparable advantages in tumor targeting drug delivery and reduced toxic side effects of therapeutic agents, nanocarriers based on biodegradable polyamino acids have attracted extensive attention for combined drug delivery in tumor immunotherapy. [30][31][32] Here, we described a pH-responsive polymeric micelle to co-deliver a STAT6 inhibitor AS1517499 (AS) and a therapeutic anti-Galectin-9 antibody (aG-9) for synergetic anti-tumor immunotherapy.…”

“…However, T cells and M2‐like macrophages throughout the body can also be affected by therapeutic agents, leading to systematic immune‐related adverse events (irAEs). [ 27–29 ]…”