https://doi.org/10.4081/ejh.2023.3784
Tumor cells-derived exosomal PD-L1 promotes the growth and invasion of lung cancer cells in vitro via mediating macrophages M2 polarization
Submitted: 27 May 2023
Accepted: 3 July 2023
Published: 1 August 2023
Accepted: 3 July 2023
Abstract Views: 739
PDF: 519
HTML: 10
HTML: 10
Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Authors
Lung cancer originating from the bronchial epithelium is the most common lung malignancy. It has been reported that programmed cell death 1 ligand 1 (PD-L1) and tumor-associated macrophages are closely related to the development of lung cancer. However, whether tumor-derived exosomal PD-L1 could mediate the regulation of macrophage polarization in lung cancer remains unclear. For this research, the level of PD-L1 in normal tissues and lung cancer tissues was evaluated using RT-qPCR. Next, the apoptosis of lung cancer cells was evaluated using flow cytometry assay. Then, the structure and morphology of vesicles were observed using transmission electron microscopy and nanoparticle tracking analysis. Later on, the internalization of exosomes by macrophage was observed using fluorescence microscopy. Our results showed that the level of PD-L1 was upregulated in tumor tissues and lung cancer cells. Knockdown of PD-L1 notably inhibited the viability, migration and invasion of lung cancer cells. In addition, lung cancer cells-derived exosomal PD-L1 could be absorbed by macrophages. Meanwhile, exosomal PD-L1 was able to promote macrophages M2 polarization. Moreover, macrophages M2 polarization induced by exosomal PD-L1 further remarkably promoted the viability, migration, invasion, and epithelial-mesenchymal transition process of lung cancer cells. Collectively, knockdown of PD-L1 notably inhibited the viability, migration and invasion of lung cancer cells. Tumor cell-derived exosomal PD-L1 could promote the growth of lung cancer cells by mediating macrophages M2 polarization. Thus, inhibiting macrophages M2 polarization might be a promoting therapy for the treatment of lung cancer.
Yoshida K, Gowers KHC, Lee-Six H, Chandrasekharan DP, Coorens T, Maughan EF, et al. Tobacco smoking and somatic mutations in human bronchial epithelium. Nature 2020;578:266-72.
DOI: https://doi.org/10.1038/s41586-020-1961-1
Yang D, Liu Y, Bai C, Wang X, Powell CA. Epidemiology of lung cancer and lung cancer screening programs in China and the United States. Cancer Lett 2020;468:82-7.
DOI: https://doi.org/10.1016/j.canlet.2019.10.009
Bersimbaev R PA, Bulgakova O, Asia K, Aripova A, Izzotti A. Radon biomonitoring and microRNA in lung cancer. Int J Mol Sci 2020;21:2154.
DOI: https://doi.org/10.3390/ijms21062154
Ruiz-Cordero R, Devine WP. Targeted therapy and checkpoint immunotherapy in lung cancer. Surg Pathol Clin 2020;13:17-33.
DOI: https://doi.org/10.1016/j.path.2019.11.002
Oser MG, Niederst MJ, Sequist LV, Engelman JA. Transformation from non-small-cell lung cancer to small-cell lung cancer: molecular drivers and cells of origin. Lancet Oncol 2015;16:e165-72.
DOI: https://doi.org/10.1016/S1470-2045(14)71180-5
de Groot P, Munden RF. Lung cancer epidemiology, risk factors, and prevention. Radiol Clin North Am 2012;50:863-76.
DOI: https://doi.org/10.1016/j.rcl.2012.06.006
Jung KJ, Jeon C, Jee SH. The effect of smoking on lung cancer: ethnic differences and the smoking paradox. Epidemiol Health 2016;38:e2016060.
DOI: https://doi.org/10.4178/epih.e2016060
Dubin S, Griffin D. Lung cancer in non-smokers. Mo Med 2020;117:375-9.
Nwagbara UI, Ginindza TG, Hlongwana KW. Lung cancer awareness and palliative care interventions implemented in low-and middle-income countries: a scoping review. BMC Public Health 2020;20:1466.
DOI: https://doi.org/10.1186/s12889-020-09561-0
Vinod SK, Hau E. Radiotherapy treatment for lung cancer: Current status and future directions. Respirology 2020;25:S61-71.
DOI: https://doi.org/10.1111/resp.13870
Steven A, Fisher SA, Robinson BW. Immunotherapy for lung cancer. Respirology 2016;21:821-33.
DOI: https://doi.org/10.1111/resp.12789
Gou Q, Dong C, Xu H, Khan B, Jin J, Liu Q, et al. PD-L1 degradation pathway and immunotherapy for cancer. Cell Death Dis 2020;11:955.
DOI: https://doi.org/10.1038/s41419-020-03140-2
Ai L, Xu A, Xu J. Roles of PD-1/PD-L1 pathway: signaling, cancer, and beyond. Adv Exp Med Biol 2020;1248:33-59.
DOI: https://doi.org/10.1007/978-981-15-3266-5_3
Li C, Zhang N, Zhou J, Ding C, Jin Y, Cui X, et al. Peptide blocking of PD-1/PD-L1 interaction for cancer immunotherapy. Cancer Immunol Res 2018;6:178-88.
DOI: https://doi.org/10.1158/2326-6066.CIR-17-0035
Yu H, Boyle TA, Zhou C, Rimm DL, Hirsch FR. PD-L1 expression in lung cancer. J Thorac Oncol 2016;11:964-75.
DOI: https://doi.org/10.1016/j.jtho.2016.04.014
Kim J, Bae JS. Tumor-associated macrophages and neutrophils in tumor microenvironment. Mediators Inflamm 2016;2016:6058147.
DOI: https://doi.org/10.1155/2016/6058147
Jaynes JM SR, Ronzetti M, Bautista W, Knotts Z, Abisoye-Ogunniyan A, et al. Mannose receptor (CD206) activation in tumor-associated macrophages enhances adaptive and innate antitumor immune responses. Sci Transl Med 2020;12:eaax6337.
DOI: https://doi.org/10.1126/scitranslmed.aax6337
Yunna C, Mengru H, Lei W, Weidong C. Macrophage M1/M2 polarization. Eur J Pharmacol 2020;877:173090.
DOI: https://doi.org/10.1016/j.ejphar.2020.173090
Orecchioni M, Ghosheh Y, Pramod AB, Ley K. Macrophage polarization: Different gene signatures in M1(LPS+) vs. classically and M2(LPS-) vs. alternatively activated macrophages. Front Immunol 2019;10:1084.
DOI: https://doi.org/10.3389/fimmu.2019.01084
Zhao S, Mi Y, Guan B, Zheng B, Wei P, Gu Y, et al. Tumor-derived exosomal miR-934 induces macrophage M2 polarization to promote liver metastasis of colorectal cancer. J Hematol Oncol 2020;13:156.
DOI: https://doi.org/10.1186/s13045-020-00991-2
Yang Y, Ye YC, Chen Y, Zhao JL, Gao CC, Han H, et al. Crosstalk between hepatic tumor cells and macrophages via Wnt/β-catenin signaling promotes M2-like macrophage polarization and reinforces tumor malignant behaviors. Cell Death Dis 2018;9:793.
DOI: https://doi.org/10.1038/s41419-018-0818-0
Tariq M, Zhang JQ, Liang GK, He QJ, Ding L, Yang B. Gefitinib inhibits M2-like polarization of tumor-associated macrophages in Lewis lung cancer by targeting the STAT6 signaling pathway. Acta Pharmacol Sin 2017;38:1501-11.
DOI: https://doi.org/10.1038/aps.2017.124
Ren W, Hou J, Yang C, Wang H, Wu S, Wu Y, et al. Extracellular vesicles secreted by hypoxia pre-challenged mesenchymal stem cells promote non-small cell lung cancer cell growth and mobility as well as macrophage M2 polarization via miR-21-5p delivery. J Exp Clin Cancer Res 2019;38:62.
DOI: https://doi.org/10.1186/s13046-019-1027-0
Gurung S, Perocheau D, Touramanidou L, Baruteau J. The exosome journey: from biogenesis to uptake and intracellular signalling. Cell Commun Signal 2021;19:47.
DOI: https://doi.org/10.1186/s12964-021-00730-1
Fan Z, Wu C, Chen M, Jiang Y, Wu Y, Mao R, et al. The generation of PD-L1 and PD-L2 in cancer cells: From nuclear chromatin reorganization to extracellular presentation. Acta Pharm Sin B 2022;12:1041-53.
DOI: https://doi.org/10.1016/j.apsb.2021.09.010
Xu F, Cui WQ, Wei Y, Cui J, Qiu J, Hu LL, et al. Astragaloside IV inhibits lung cancer progression and metastasis by modulating macrophage polarization through AMPK signaling. J Exp Clin Cancer Res 2018;37:207.
DOI: https://doi.org/10.1186/s13046-018-0878-0
Xia Q, Wang Q, Lin F, Wang J. miR-125a-5p-abundant exosomes derived from mesenchymal stem cells suppress chondrocyte degeneration via targeting E2F2 in traumatic osteoarthritis. Bioengineered 2021;12:11225-38.
DOI: https://doi.org/10.1080/21655979.2021.1995580
Tan D, Li G, Zhang P, Peng C, He B. LncRNA SNHG12 in extracellular vesicles derived from carcinoma-associated fibroblasts promotes cisplatin resistance in non-small cell lung cancer cells. Bioengineered 2022;13:1838-57.
DOI: https://doi.org/10.1080/21655979.2021.2018099
Kim DH, Kim H, Choi YJ, Kim SY, Lee JE, Sung KJ, et al. Exosomal PD-L1 promotes tumor growth through immune escape in non-small cell lung cancer. Exp Mol Med 2019;51:1-13.
DOI: https://doi.org/10.1038/s12276-019-0295-2
Huang WC, Kuo KT, Wang CH, Yeh CT, Wang Y. Cisplatin resistant lung cancer cells promoted M2 polarization of tumor-associated macrophages via the Src/CD155/MIF functional pathway. J Exp Clin Cancer Res 2019;38:180.
DOI: https://doi.org/10.1186/s13046-019-1166-3
Espinosa Gonzalez M, Volk-Draper L, Bhattarai N, Wilber A, Ran S. Th2 cytokines IL-4, IL-13, and IL-10 promote differentiation of pro-lymphatic progenitors derived from bone marrow myeloid precursors. Stem Cells Dev 2022;31:322-33.
DOI: https://doi.org/10.1089/scd.2022.0004
Naylor EC, Desani JK, Chung PK. Targeted therapy and immunotherapy for lung cancer. Surg Oncol Clin N Am 2016;25:601-9.
DOI: https://doi.org/10.1016/j.soc.2016.02.011
Xia L, Liu Y, Wang Y. PD-1/PD-L1 Blockade therapy in advanced non-small-cell lung cancer: current status and future directions. Oncologist 2019;24:S31-S41.
DOI: https://doi.org/10.1634/theoncologist.2019-IO-S1-s05
Hashimoto K, Nishimura S, Shinyashiki Y, Ito T, Kakinoki R, Akagi M. Clinicopathological assessment of PD-1/PD-L1 immune checkpoint expression in desmoid tumors. Eur J Histochem 2023;67:3688.
DOI: https://doi.org/10.4081/ejh.2023.3688
Hashimoto K, Nishimura S, Ito T, Kakinoki R, Akagi M. Immunohistochemical expression and clinicopathological assessment of PD-1, PD-L1, NY-ESO-1, and MAGE-A4 expression in highly aggressive soft tissue sarcomas. Eur J Histochem 2022;66:3393.
DOI: https://doi.org/10.4081/ejh.2022.3393
Hashimoto K, Nishimura S, Ito T, Akagi M. Characterization of PD-1/PD-L1 immune checkpoint expression in soft tissue sarcomas. Eur J Histochem 2021;65:3203.
DOI: https://doi.org/10.4081/ejh.2021.3203
Zhang M, Li G, Wang Y, Wang Y, Zhao S, Haihong P, et al. PD-L1 expression in lung cancer and its correlation with driver mutations: a meta-analysis. Sci Rep 2017;7:10255.
DOI: https://doi.org/10.1038/s41598-017-10925-7
Huang Q, Wu X, Wang Z, Chen X, Wang L, Lu Y, et al. The primordial differentiation of tumor-specific memory CD8(+) T cells as bona fide responders to PD-1/PD-L1 blockade in draining lymph nodes. Cell 2022;185:4049-66.e25.
DOI: https://doi.org/10.1016/j.cell.2022.09.020
Chen X, Gao A, Zhang F, Yang Z, Wang S, Fang Y, et al. ILT4 inhibition prevents TAM- and dysfunctional T cell-mediated immunosuppression and enhances the efficacy of anti-PD-L1 therapy in NSCLC with EGFR activation. Theranostics 2021;11:3392-416.
DOI: https://doi.org/10.7150/thno.52435
Pritchard A TS, Wang Y, Hough K, Khan S, Strenkowski J, et al. Lung tumor cell-derived exosomes promote M2 macrophage polarization. Cells 2020;9:1303.
DOI: https://doi.org/10.3390/cells9051303
Liu Q, Yang C, Wang S, Shi D, Wei C, Song J, et al. Wnt5a-induced M2 polarization of tumor-associated macrophages via IL-10 promotes colorectal cancer progression. Cell Commun Signal 2020;18:51.
DOI: https://doi.org/10.1186/s12964-020-00557-2
Wei J, Wu L, Yang S, Zhang C, Feng L, Wang M, et al. E-cadherin to N-cadherin switching in the TGF-β1 mediated retinal pigment epithelial to mesenchymal transition. Exp Eye Res 2022;220:109085.
DOI: https://doi.org/10.1016/j.exer.2022.109085
Taki M, Abiko K, Ukita M, Murakami R, Yamanoi K, Yamaguchi K, et al. Tumor immune microenvironment during epithelial-mesenchymal transition. Clin Cancer Res 2021;27:4669-79.
DOI: https://doi.org/10.1158/1078-0432.CCR-20-4459
Kuburich NA, den Hollander P, Pietz JT, Mani SA. Vimentin and cytokeratin: Good alone, bad together. Semin Cancer Biol 2022;86:816-26.
DOI: https://doi.org/10.1016/j.semcancer.2021.12.006
Menju T, Date H. Lung cancer and epithelial-mesenchymal transition. Gen Thorac Cardiovasc Surg 2021;69:781-9.
DOI: https://doi.org/10.1007/s11748-021-01595-4
Ethics Approval
this study was approved by Ethics Committee of the Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, with approval document no. 2021008Supporting Agencies
Foundation of Zhejiang Provincial Scientific Research on Traditional Chinese Medicine , General Project Funds from the Health Department of Zhejiang Province, Foundation for Natural Science of Zhejiang ProvinceHow to Cite
Lu, X., Shen, J., Huang, S., Liu, D., & Wang, H. (2023). Tumor cells-derived exosomal PD-L1 promotes the growth and invasion of lung cancer cells <em>in vitro via</em> mediating macrophages M2 polarization. European Journal of Histochemistry, 67(3). https://doi.org/10.4081/ejh.2023.3784
Copyright (c) 2023 The Author(s)
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
PAGEPress has chosen to apply the Creative Commons Attribution NonCommercial 4.0 International License (CC BY-NC 4.0) to all manuscripts to be published.
Similar Articles
- A. Gonelli, D. Milani, E. Rimondi, R. Voltan, V. Grill, C. Celeghini, Activation of PKC-e counteracts maturation and apoptosis of HL-60 myeloid leukemic cells in response to TNF family members , European Journal of Histochemistry: Vol. 53 No. 3 (2009)
- Zhao Zhang, Hongming Fan, William Richardson, Bruce Z. Gao, Tong Ye, Management of autofluorescence in formaldehyde-fixed myocardium: choosing the right treatment , European Journal of Histochemistry: Vol. 67 No. 4 (2023)
- Bin Ma, Changfu Yin, Dailun Hu, Mark Newman, Philip K. Nicholls, Zhanjun Wu, Wayne K. Greene, Zhongli Shi, Distribution of non-myelinating Schwann cells and their associations with leukocytes in mouse spleen revealed by immunofluorescence staining , European Journal of Histochemistry: Vol. 62 No. 2 (2018)
- S Matsubara, T Kato, K Oshikawa, T Yamada, T Takayama, T Koike, T Watanabe, A Izumi, I Sato, Glucose-6-phosphate dehydrogenase in rat lung alveolar epithelial cells. An ultrastructural enzyme-cytochemical study , European Journal of Histochemistry: Vol. 46 No. 3 (2002)
- CarloAlberto Redi, Light microscopy - Methods and protocols , European Journal of Histochemistry: Vol. 55 No. 4 (2011)
- Carlo Alberto Redi, DNA damage detection In situ, ex vivo and In vivo - Methods and protocols , European Journal of Histochemistry: Vol. 55 No. 2 (2011)
- Carlo Alberto Redi, A picture is worth a thousand tables - graphics in life sciences , European Journal of Histochemistry: Vol. 57 No. 3 (2013)
- L. Benerini Gatta, M. Cadei, P. Balzarini, S. Castriciano, R. Paroni, A. Verzeletti, V. Cortellini, F. De Ferrari, P. Grigolato, Application of alternative fixatives to formalin in diagnostic pathology , European Journal of Histochemistry: Vol. 56 No. 2 (2012)
- Carlo Alberto Redi, Regenerative medicine and cell therapy , European Journal of Histochemistry: Vol. 57 No. 2 (2013)
- CarloAlberto Redi, Adult stem cells - Biology and methods of analysis , European Journal of Histochemistry: Vol. 55 No. 4 (2011)
<< < 49 50 51 52 53 54 55 56 57 58 > >>
You may also start an advanced similarity search for this article.
Publication Facts
Metric
This article
Other articles
Peer reviewers
2
2.4
Reviewer profiles N/A
Author statements
Author statements
This article
Other articles
Data availability
N/A
16%
External funding
N/A
32%
Competing interests
N/A
11%
Metric
This journal
Other journals
Articles accepted
57%
33%
Days to publication
65
145
- Editor & editorial board
- profiles
- Academic society
- N/A
- Publisher
- PAGEPress Publications, Pavia, Italy
To learn about these publication facts, click 
PF is maintained by the Public Knowledge Project
