Covid-19 Research

Review Article

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The Cellular Crosstalk between the Endothelial Cells and Immune Cells in the Metastasis of NSCLC

Medicine Group    Start Submission

Wang J, Huang Y, Jin Y, Liu G

Volume6-Issue11
Dates: Received: 2025-10-15 | Accepted: 2025-11-04 | Published: 2025-11-05
Pages: 1643-1654

Abstract

Background: Bone and brain metastasis are common in the NSCLC, and tumor environment has played a vital role in the metastasis, endothelial cells are a key component of the tumor microenvironment and its role in the development need to be investigated.

Methods: We collected three scRNA‑Seq datasets: GSE254379, GSE131907 and GSE225209 associated with the metastasis of lung cancer, and we integrated three datasets. Dimensionality reduction, clustering, and visualization (t - SNE, UMAP) were conducted, leading to the annotation of six major cell types (T cells, B/plasma cells, ECs, myeloid cells, fibroblasts, epithelial cells) using canonical markers. Subpopulation analysis, differential gene expression, and enrichment analysis were performed for each major cell type using the SCP package, with cell clusters annotated via established marker databases (CellMarker, PanglaoDB). The distribution preference of cell categories across tissues was assessed using odds ratios. Cell-cell communication was inferred using CellChat, analysing multiple signalling categories.

Results: We integrated three single-cell databases of metastasis-related NSCLC (GSE254379, GSE131907 and GSE225209). And we found that he arterial ECs, CD8 + T cycling T cells, MZB1 + plasma cells, MMP9 + macrophages were most associated with the bone metastasis. The CD8 + T GZMB cells, RPL + B cells, RPL + B cells were more abundant in the brain metastasis tissue. Compared with other immune cells, bidirectional interactions became much more in ECs and B cells. In cellular interactions, APP-CD74 plays an important role in immune cells and tumors.

Conclusion: APP - CD74 might mediate B cells and endothelial cells to play a vital role in tumor development.

FullText HTML FullText PDF DOI: 10.37871/jbres2217


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Copyright

© 2025 Wang J, et al. Distributed under Creative Commons CC-BY 4.0

How to cite this article

Wang J, Huang Y, Jin Y, Liu G. The Cellular Crosstalk between the Endothelial Cells and Immune Cells in the Metastasis of NSCLC. J Biomed Res Environ Sci. 2025 Nov 05; 6(11): 1643-1654. doi: 10.37871/ jbres2217, Article ID: JBRES2217, Available at: https://www.jelsciences.com/articles/jbres2217.pdf


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References


  1. Claesson-Welsh L, Dejana E, McDonald DM. Permeability of the Endothelial Barrier: Identifying and Reconciling Controversies. Trends Mol Med. 2021 Apr;27(4):314-331. doi: 10.1016/j.molmed.2020.11.006. Epub 2020 Dec 10. PMID: 33309601; PMCID: PMC8005435.
  2. Xu K, Wang H, Zou YX, Zhang HH, Wang YN, Ren XR, Wang HQ, Xu YH, Li JJ, Tang H, He C, Wei S, Tian T, Li LL, Zhou H, Xu LJ, Fang JW, Guo C, Yang JX, Zhou YY, Zhang ZH, Pan YY. Distinct fibroblast subpopulations associated with bone, brain or intrapulmonary metastasis in advanced non-small-cell lung cancer. Clin Transl Med. 2024 Mar;14(3):e1605. doi: 10.1002/ctm2.1605. PMID: 38445456; PMCID: PMC10915739.
  3. Wang Y, Chen R, Wa Y, Ding S, Yang Y, Liao J, Tong L, Xiao G. Tumor Immune Microenvironment and Immunotherapy in Brain Metastasis From Non-Small Cell Lung Cancer. Front Immunol. 2022 Feb 17;13:829451. doi: 10.3389/fimmu.2022.829451. PMID: 35251014; PMCID: PMC8891382.
  4. Brouns AJWM, Hendriks LEL, Robbesom-van den Berge IJ, Driessen AJHM, Roemen GMJM, van Herpen BLJ, Dekkers Z, Heitzer B, Leunissen DJG, Moonen L, Lunde R, Westenend M, van Driel M, Speel EM, Dingemans AC. Association of RANKL and EGFR gene expression with bone metastases in patients with metastatic non-small cell lung cancer. Front Oncol. 2023 May 5;13:1145001. doi: 10.3389/fonc.2023.1145001. PMID: 37213294; PMCID: PMC10196450.
  5. Mashouri L, Yousefi H, Aref AR, Ahadi AM, Molaei F, Alahari SK. Exosomes: composition, biogenesis, and mechanisms in cancer metastasis and drug resistance. Mol Cancer. 2019 Apr 2;18(1):75. doi: 10.1186/s12943-019-0991-5. PMID: 30940145; PMCID: PMC6444571.
  6. Su D, Wu G, Xiong R, Sun X, Xu M, Mei Y, Wu X. Tumor Immune Microenvironment Characteristics and Their Prognostic Value in Non-Small-Cell Lung Cancer. Front Oncol. 2021 Mar 3;11:634059. doi: 10.3389/fonc.2021.634059. PMID: 33747957; PMCID: PMC7966704.
  7. Zhang W, Xu J, Fang H, Tang L, Chen W, Sun Q, Zhang Q, Yang F, Sun Z, Cao L, Wang Y, Guan X. Endothelial cells promote triple-negative breast cancer cell metastasis via PAI-1 and CCL5 signaling. FASEB J. 2018 Jan;32(1):276-288. doi: 10.1096/fj.201700237RR. Epub 2017 Sep 12. PMID: 28899878.
  8. Bejarano L, Kauzlaric A, Lamprou E, Lourenco J, Fournier N, Ballabio M, Colotti R, Maas R, Galland S, Massara M, Soukup K, Lilja J, Brouland JP, Hottinger AF, Daniel RT, Hegi ME, Joyce JA. Interrogation of endothelial and mural cells in brain metastasis reveals key immune-regulatory mechanisms. Cancer Cell. 2024 Mar 11;42(3):378-395.e10. doi: 10.1016/j.ccell.2023.12.018. Epub 2024 Jan 18. PMID: 38242126.
  9. Mao X, Xu J, Wang W, Liang C, Hua J, Liu J, Zhang B, Meng Q, Yu X, Shi S. Crosstalk between cancer-associated fibroblasts and immune cells in the tumor microenvironment: new findings and future perspectives. Mol Cancer. 2021 Oct 11;20(1):131. doi: 10.1186/s12943-021-01428-1. PMID: 34635121; PMCID: PMC8504100.
  10. Maia A, Schöllhorn A, Schuhmacher J, Gouttefangeas C. CAF-immune cell crosstalk and its impact in immunotherapy. Semin Immunopathol. 2023 Mar;45(2):203-214. doi: 10.1007/s00281-022-00977-x. Epub 2022 Dec 8. PMID: 36480035; PMCID: PMC10121542.
  11. Baker AT, Abuwarwar MH, Poly L, Wilkins S, Fletcher AL. Cancer-Associated Fibroblasts and T Cells: From Mechanisms to Outcomes. J Immunol. 2021 Jan 15;206(2):310-320. doi: 10.4049/jimmunol.2001203. PMID: 33397745.
  12. Luo G, He Y, Yu X. Bone Marrow Adipocyte: An Intimate Partner With Tumor Cells in Bone Metastasis. Front Endocrinol (Lausanne). 2018 Jun 22;9:339. doi: 10.3389/fendo.2018.00339. PMID: 30013512; PMCID: PMC6036292.
  13. Alameddine RS, Hamieh L, Shamseddine A. From sprouting angiogenesis to erythrocytes generation by cancer stem cells: evolving concepts in tumor microcirculation. Biomed Res Int. 2014;2014:986768. doi: 10.1155/2014/986768. Epub 2014 Aug 4. PMID: 25162040; PMCID: PMC4138761.
  14. Sivori S, Pende D, Quatrini L, Pietra G, Della Chiesa M, Vacca P, Tumino N, Moretta F, Mingari MC, Locatelli F, Moretta L. NK cells and ILCs in tumor immunotherapy. Mol Aspects Med. 2021 Aug;80:100870. doi: 10.1016/j.mam.2020.100870. Epub 2020 Aug 13. PMID: 32800530.
  15. Pritchard A, Tousif S, Wang Y, Hough K, Khan S, Strenkowski J, Chacko BK, Darley-Usmar VM, Deshane JS. Lung Tumor Cell-Derived Exosomes Promote M2 Macrophage Polarization. Cells. 2020 May 24;9(5):1303. doi: 10.3390/cells9051303. PMID: 32456301; PMCID: PMC7290460.
  16. Guo X, Xu L, Nie L, Zhang C, Liu Y, Zhao R, Cao J, Tian L, Liu M. B cells in head and neck squamous cell carcinoma: current opinion and novel therapy. Cancer Cell Int. 2024 Jan 20;24(1):41. doi: 10.1186/s12935-024-03218-3. PMID: 38245714; PMCID: PMC10799521.
  17. Heidegger I, Fotakis G, Offermann A, Goveia J, Daum S, Salcher S, Noureen A, Timmer-Bosscha H, Schäfer G, Walenkamp A, Perner S, Beatovic A, Moisse M, Plattner C, Krogsdam A, Haybaeck J, Sopper S, Thaler S, Keller MA, Klocker H, Trajanoski Z, Wolf D, Pircher A. Comprehensive characterization of the prostate tumor microenvironment identifies CXCR4/CXCL12 crosstalk as a novel antiangiogenic therapeutic target in prostate cancer. Mol Cancer. 2022 Jun 18;21(1):132. doi: 10.1186/s12943-022-01597-7. PMID: 35717322; PMCID: PMC9206324.
  18. Ma R, Zhou X, Zhai X, Wang C, Hu R, Chen Y, Shi L, Fang X, Liao Y, Ma L, Jiang M, Wu J, Wang R, Chen J, Cao T, Du G, Zhao Y, Wu W, Chen H, Li S, Lian Q, Guo G, Xiao J, Hutchins AP, Yuan P. Single-cell RNA sequencing reveals immune cell dysfunction in the peripheral blood of patients with highly aggressive gastric cancer. Cell Prolif. 2024 May;57(5):e13591. doi: 10.1111/cpr.13591. Epub 2024 Feb 6. PMID: 38319150; PMCID: PMC11056698.
  19. Wang Z, Wang B, Feng Y, Ye J, Mao Z, Zhang T, Xu M, Zhang W, Jiao X, Zhang Q, Zhang Y, Cui B. Targeting tumor-associated macrophage-derived CD74 improves efficacy of neoadjuvant chemotherapy in combination with PD-1 blockade for cervical cancer. J Immunother Cancer. 2024 Aug 6;12(8):e009024. doi: 10.1136/jitc-2024-009024. PMID: 39107132; PMCID: PMC11308911.
  20. Liu B, Li F, Wang Y, Gao X, Li Y, Wang Y, Zhou H. APP-CD74 axis mediates endothelial cell-macrophage communication to promote kidney injury and fibrosis. Front Pharmacol. 2024 Sep 16;15:1437113. doi: 10.3389/fphar.2024.1437113. PMID: 39351084; PMCID: PMC11439715.
  21. Chen G, Wang W, Wei X, Chen Y, Peng L, Qu R, Luo Y, He S, Liu Y, Du J, Lu R, Li S, Fan C, Chen S, Dai Y, Yang L. Single-cell transcriptomic analysis reveals that the APP-CD74 axis promotes immunosuppression and progression of testicular tumors. J Pathol. 2024 Nov;264(3):250-269. doi: 10.1002/path.6343. Epub 2024 Aug 19. PMID: 39161125.
  22. Xuan Z, Wu Z, Cheng L, Jiang J, Zhang Y, Xia Y. SCGB3A1-Epi and KLK10-Epi Crosstalk With Fibroblasts Promotes Liver Metastasis of Breast Cancer and Pancreatic Ductal Adenocarcinoma. Cancer Med. 2025 May;14(9):e70904. doi: 10.1002/cam4.70904. PMID: 40357856; PMCID: PMC12070254.
  23. Ma C, Chen J, Ji J, Zheng Y, Liu Y, Wang J, Chen T, Chen H, Chen Z, Zhou Q, Hou C, Ke Y. Therapeutic modulation of APP-CD74 axis can activate phagocytosis of TAMs in GBM. Biochim Biophys Acta Mol Basis Dis. 2024 Dec;1870(8):167449. doi: 10.1016/j.bbadis.2024.167449. Epub 2024 Aug 5. PMID: 39111632.


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