Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Mar 6:2023:7971306.
doi: 10.1155/2023/7971306. eCollection 2023.

Correlation between Macrophage Polarization and PD-L1-Related Tumor Microenvironmental Alteration and Metastasis in Pancreatic Ductal Adenocarcinoma

Jiangning Gu  1 , Feng Gao  2 , Bin Fan  3 , Shiqi Xu  1 , Haifeng Luo  1 , Jie Zhang  4 , Qi Jiang  5 , Chenqi Wang  1 , Guang Tan  1 , Wenjing Qi  5 , Jian Du  1 , Siqian Huang  5 , Xiaohong Sun  6 , Dan Chen  5
Affiliations

Correlation between Macrophage Polarization and PD-L1-Related Tumor Microenvironmental Alteration and Metastasis in Pancreatic Ductal Adenocarcinoma

Jiangning Gu et al. J Oncol. .

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with a poor prognosis; nearly 80% patients have regional or distant metastasis when diagnosed. Tumor microenvironment (TME) alteration and epithelial-to-mesenchymal transition (EMT) have been reported to play a key role in cancer metastasis. However, the correlation between TME and EMT was poorly studied in PDAC. This study aims to explore the correlation between EMT markers and TME alteration, mainly including macrophage polarization and PD-L1 expression change, in primary and metastatic PDAC tissues by immunohistochemistry. The results indicated that macrophage polarization was found in metastases with the number of M1 macrophages (CD86+) decreased and M2 (CD163+) increased, though PD-L1 expression did not have a significant alteration. Compared to primary tumors, E-cadherin was significantly lower, while snail was higher, while no difference was found with N-cadherin and ZEB1. Correlation analysis indicated that snail, but not ZEB1, E-cadherin, or N-cadherin, was highly correlated with macrophage polarization. To conclude, the number of CD86+ M1 macrophages was increased while CD163+ M2 macrophages decreased in metastases, with no significant alteration of PD-L1 expression compared to primary tumors. EMT markers-Snail and E-cadherin-but not ZEB1 or N-cadherin, were found to be higher/lower in metastases, which mean that EMT played an important role in PDAC metastasis. Further analysis indicated that snail was highly correlated with M1 to M2 macrophage polarization, which prompted that EMT may be one reason for macrophage polarization induced TME alteration in PDAC metastasis.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no conflicts of interest.

Figures

Figure 1
Figure 1
Representative immunohistochemical image and the number of CD86 and CD163 in primary tumors and metastatic site.
Figure 2
Figure 2
Representative immunohistochemical image of PD-L1 in primary tumors and metastatic site.
Figure 3
Figure 3
Immunohistochemistry and quantification of EMT markers in in primary tumors and metastatic site. (a) Representative immunohistochemical image of E-cadherin in primary tumors and metastatic site. (b) Representative immunohistochemical image of ZEB1 in primary tumors and metastatic site. (c) Representative immunohistochemical image of N-cadherin in primary tumors and metastatic site. (d) Representative immunohistochemical image of Snail in primary tumors and metastatic site. ∗∗∗P < 0.001; ns, not significant.
Figure 4
Figure 4
Spearman correlation analysis between the number of M2 macrophages infiltration in metastatic site and EMT markers. (a) There was no significant correlation between the number of M2 macrophages infiltration and E-cadherin in metastases. (b) Significant correlation was found between the number of M2 macrophages infiltration and E-cadherin in metastatic site.
See this image and copyright information in PMC

References

    1. Siegel R. L., Miller K. D., Fuchs H. E., Jemal A. Cancer statistics. CA: A Cancer Journal for Clinicians . 2021;71(1):7–33. doi: 10.3322/caac.21654. - DOI - PubMed
    1. Yuan X., Li Y., Zhang A. Z., et al. Tumor-associated macrophage polarization promotes the progression of esophageal carcinoma. Aging (Albany NY) . 2020;13(2):2049–2072. doi: 10.18632/aging.202201. - DOI - PMC - PubMed
    1. Hu J. M., Liu K., Liu J. H., et al. The increased number of tumor-associated macrophage is associated with overexpression of VEGF-C, plays an important role in Kazakh ESCC invasion and metastasis. Experimental and Molecular Pathology . 2017;102(1):15–21. doi: 10.1016/j.yexmp.2016.12.001. - DOI - PubMed
    1. Gellrich F. F., Schmitz M., Beissert S., Meier F. Anti-PD-1 and novel combinations in the treatment of melanoma—an update. Journal of Clinical Medicine . 2020;9(1):p. 223. doi: 10.3390/jcm9010223. - DOI - PMC - PubMed
    1. Liu S.-Y., Wu Y.-L. Tislelizumab: an investigational anti-PD-1 antibody for the treatment of advanced non-small cell lung cancer (NSCLC) Expert Opinion on Investigational Drugs . 2020;29(12):1355–1364. doi: 10.1080/13543784.2020.1833857. - DOI - PubMed