Table 4.
Summary of the role of macrophages and neutrophils in the TME of CCA
| Cells | The research direction | Result | Reference | Reference number |
|---|---|---|---|---|
| Macrophages | The immune mechanism | The spatial distribution of TANs and TAMs correlated with each other in samples from patients with intrahepatic CCA. STAT3 is an important molecule in the interaction between TANs and TAMs to promote the progression of ICC. | Zhou et al. (2021) | 98 |
| Macrophages | Immunotherapy | Periostin secreted by intrahepatic CCA stem cells (ICSCs) promotes the recruitment of TAMs in the TME, providing a new target for immunotherapy. | Zeng et al. (2018) | 149 |
| Macrophages | The immune mechanism | The presence of macrophages exacerbates the cytotoxicity, DNA damage and ROS generation of 1,2-Dichloropropane (1,2-DCP) on cholangiocytes, which may be the underlying mechanism of 1,2-DCP-induced carcinogenesis of CCAs. | Ekuban et al. (2021) | 150 |
| Macrophages | The immune mechanism | M2-TAM may promote CCA metastasis through EMT process in the early stage of live Hodgella opioides (Ov)-induced CCA (CCA). High density of M2 TAMs in patient CCA tissue was significantly associated with extrahepatic metastasis. | Thanee et al. (2015) | 92 |
| Macrophages | The immune mechanism | M2 macrophage-derived TGFβ1 promotes CCA progression and chemoresistance through aPKCɩ-mediated NF-κB signaling pathway. CCL5 secreted by CCA cells undergoing aPKCɩ-induced EMT in turn regulates macrophage recruitment and polarization. | Yang et al. (2022) | 151 |
| Macrophages | The immune mechanism | The lncRNA PCAT6 (PCAT6) plays an important role in regulating the function and differentiation of immune cells. In a CCA xenograft mouse model, the PCAT6/miR-326/RohA pathway regulates M2 macrophage polarization. | Tu et al. (2020) | 88 |
| Macrophages | The immune mechanism | Interaction between M2 macrophages and ICC, M2 polarized macrophages induce EMT in CCA cells via IL-10/STAT3. | Yuan et al. (2020) | 152 |
| Macrophages | The immune mechanism | In the ICC mouse model, the recruitment of hepatic macrophage-derived Wnt3a due to inflammation may promote the malignant transformation of hepatocytes into ICC cells. | Saito et al. (2018) | 95 |
| Macrophages | Immunotherapy | The number of CD68+ TAMs infiltrated in tumor tissue was associated with OS in patients undergoing resection. Anti-GM-CSF therapy can relieve the establishment of an immunosuppressive microenvironment through the repolarization of TAMs and MDSCs. | Ruffolo et al. (2022) | 99 |
| Macrophages | The immune mechanism | CCA-sphere conditioned medium constructs an immune niche suitable for the growth of CCA by regulating macrophages. | Raggi et al. (2017) | 153 |
| Macrophages | The immune mechanism | Exosomes are important mediators of the crosstalk between tumor cells and the tumor microenvironment. miR-183-5p upregulates PD-L1 expression in macrophages through the miR-183-5p/PTEN/AKT/PD-L1 pathway, mediating CCA Immunosuppression in the process. | Luo et al. (2022) | 97 |
| Macrophages | The immune mechanism | The TAM-secreted exosome Circ_002056 regulates the proliferation, migration and invasion of CCA cells in the tumor microenvironment through the Circ_002056/miR-432-5p/E2F3 axis. CircRNAs produced by tumor-associated macrophages can serve as a new molecular target for clinical therapy. | Chen et al. (2022) | 96 |
| Macrophages | Prognostic marker | Immunohistochemical techniques were used to assess the abundance of TAMs in tumor samples from patients with intrahepatic CCA. The number of TAMs in the tumor invasive front is a meaningful prognostic marker in routine histopathological evaluation. | Atanasov et al. (2017) | 100 |
| Macrophages | Prognostic marker | In ICC patient tumor samples, the number of macrophages was positively correlated with the number of blood vessels and regulatory T cells, but not with the OS of the patients. | Hasita et al. (2010) | 154 |
| Macrophages | Prognostic marker | Intratumoral M2 macrophages are associated with OS in patients with CCA, suggesting the possibility of targeting macrophages for therapy. | Kunk et al. (2021) | 155 |
| Macrophages | The immune mechanism | When ICC cells were co-cultured with M2-TAMs, the core cytokines (GM-CSF, TNF-α, ICAM-1, IL-6) secreted by M2-TAMs activated the AKT3/PRAS40 signaling pathway to promote EMT in ICC cells. | Sun et al. (2020) | 93 |
| Macrophages | The immune mechanism | 1,2-DCP stimulates macrophages to induce high expression of the pro-inflammatory factor TNF-α, thereby inducing CCA. | Zong et al. (2019) | 156 |
| Macrophages | The immune mechanism | Compared with normal liver tissue, Wnt mRNA was significantly elevated in CCA tissue. LPS induces upregulation of Wnt3 mRNA in macrophages and induces CCA through the Wnt/β-catenin pathway. | Loilome et al. (2014) | 157 |
| Neutrophils | The immune mechanism | Overexpression of CXCL5 in CCA recruits neutrophils to aggregate and promote ICC growth and metastasis. | Zhou et al. (2014) | 82 |
| Neutrophils | Prognostic marker | Analysis of different microanatomical regions of intrahepatic CCA by tissue microarray and immunohistochemistry demonstrated that neutrophils were an independent factor for evaluating the prognosis of patients with intrahepatic CCA. | Gu et al. (2012) | 83 |
| Neutrophils | Immunotherapy | Methotrexate-containing plasma membrane microvesicles induce neutrophil aggregation in eCCA and relieve obstructive eCCA. | Gao et al. (2020) | 81 |
| Neutrophils | Prognostic marker | CD15 neutrophil staining was performed on tissue sections by immunohistochemical staining. The level of neutrophils in CCA tissues was higher than that in adjacent tissues. The expression of CD15 was significantly associated with DFS and OS in patients with CCA. | Mao et al. (2015) | 84 |