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2000
Volume 20, Issue 2
  • ISSN: 1574-8928
  • E-ISSN: 2212-3970

Abstract

Esophageal carcinoma, a lethal malignancy with limited treatment options and poor prognosis, necessitates understanding its underlying mechanisms and identifying novel therapeutic targets. Recent studies have highlighted the critical role of the immune microenvironment in esophageal carcinoma, particularly the interplay between tumor cells and immune cells mediated by exosomes and their cargos. Exosomes, small extracellular vesicles secreted by various cells, including tumor cells, facilitate intercellular communication by transferring bioactive molecules such as proteins, nucleic acids, and lipids to recipient cells. In the context of esophageal carcinoma, tumor-derived exosomes have been shown to play a significant role in shaping the immune microenvironment. In esophageal carcinoma, exosomal cargos have been found to modulate immune cell function and impact tumor progression. These cargos can carry immune inhibitory molecules, such as programmed death-ligand 1 (PD-L1), to suppress T-cell activity and promote immune evasion by tumor cells. Furthermore, exosomal cargos can activate antigen-presenting cells, enhancing their ability to present tumor-specific antigens to T cells and thereby promoting anti-tumor immune responses. Additionally, the cargos of exosomes have been implicated in the induction of immune regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) within the esophageal carcinoma microenvironment. These immunosuppressive effectors inhibit the activity of T cells, contributing to tumor immune evasion and resistance to immune therapies. In summary, exosomes and their cargo play a crucial role in the immune microenvironment of esophageal carcinoma. Understanding the mechanisms by which exosomal cargos regulate immune cell function and tumor progression may reveal novel therapeutic targets for this devastating disease.

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2024-01-03
2025-07-27

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References

  1. SungH. FerlayJ. SiegelR.L. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.CA Cancer J. Clin.202171320924910.3322/caac.21660 33538338
     [Google Scholar]
  2. AjaniJ.A. D’AmicoT.A. BentremD.J. Esophageal and esophagogastric junction cancers, version 2.2023, NCCN clinical practice guidelines in oncology.J. Natl. Compr. Canc. Netw.202321439342210.6004/jnccn.2023.0019 37015332
     [Google Scholar]
  3. YanC. HuangH. ZhengZ. Spatial distribution of tumor-infiltrating T cells indicated immune response status under chemoradiotherapy plus PD-1 blockade in esophageal cancer.Front. Immunol.202314113805410.3389/fimmu.2023.1138054 37275884
     [Google Scholar]
  4. HeJ.Z. ChenY. ZengF.M. Spatial analysis of stromal signatures identifies invasive front carcinoma-associated fibroblasts as suppressors of anti-tumor immune response in esophageal cancer.J. Exp. Clin. Cancer Res.202342113610.1186/s13046‑023‑02697‑y 37254126
     [Google Scholar]
  5. ZhangS. ZhangS. MaX. Intratumoral microbiome impacts immune infiltrates in tumor microenvironment and predicts prognosis in esophageal squamous cell carcinoma patients.Front. Cell. Infect. Microbiol.202313116579010.3389/fcimb.2023.1165790 37180444
     [Google Scholar]
  6. ZhangL. WangX. LiY. c‐Myb facilitates immune escape of esophageal adenocarcinoma cells through the miR‐145‐5p/SPOP/PD‐L1 axis.Clin. Transl. Med.2021119e46410.1002/ctm2.464 34586738
     [Google Scholar]
  7. LiR. HuangB. TianH. SunZ. Immune evasion in esophageal squamous cell cancer: From the perspective of tumor microenvironment.Front. Oncol.202312109671710.3389/fonc.2022.1096717 36698392
     [Google Scholar]
  8. JingZ. ChenK. GongL. The significance of exosomes in pathogenesis, diagnosis, and treatment of esophageal cancer.Int. J. Nanomedicine2021166115612710.2147/IJN.S321555 34511909
     [Google Scholar]
  9. LiB. SongT.N. WangF.R. Tumor-derived exosomal HMGB1 promotes esophageal squamous cell carcinoma progression through inducing PD1+ TAM expansion.Oncogenesis2019831710.1038/s41389‑019‑0126‑2 30796203
     [Google Scholar]
  10. MatsumotoY. KanoM. MurakamiK. Tumor‐derived exosomes influence the cell cycle and cell migration of human esophageal cancer cell lines.Cancer Sci.2020111124348435810.1111/cas.14660 32969511
     [Google Scholar]
  11. SiM.Y. RaoD.Y. XiaY. Role of exosomal noncoding RNA in esophageal carcinoma.Front. Oncol.202313112689010.3389/fonc.2023.1126890 37234976
     [Google Scholar]
  12. MaJ. XiaoY. TianB. Genome-wide analyses of long non-coding RNA expression profiles and functional network analysis in esophageal squamous cell carcinoma.Sci. Rep.201991916210.1038/s41598‑019‑45493‑5 31235759
     [Google Scholar]
  13. ZhaoF. LiZ. DongZ. Exploring the potential of exosome-related LncRNA pairs as predictors for immune microenvironment, survival outcome, and microbiotain landscape in esophageal squamous cell carcinoma.Front. Immunol.20221391815410.3389/fimmu.2022.918154 35880180
     [Google Scholar]
  14. LiL. WangC. LiQ. Exosomes as a modulator of immune resistance in human cancers.Cytokine Growth Factor Rev.20237313514910.1016/j.cytogfr.2023.07.007 37543438
     [Google Scholar]
  15. ZhaoL. YuL. WangX. Mechanisms of function and clinical potential of exosomes in esophageal squamous cell carcinoma.Cancer Lett.202355321599310.1016/j.canlet.2022.215993 36328162
     [Google Scholar]
  16. ZhuQ. HuangL. YangQ. Metabolomic analysis of exosomal-markers in esophageal squamous cell carcinoma.Nanoscale20211339164571646410.1039/D1NR04015D 34648610
     [Google Scholar]
  17. WeiF. LiY. The emerging roles of exosome-derived noncoding RNAs in the tumor immune microenvironment and their future applications.Biomed. Pharmacother.202215611386310.1016/j.biopha.2022.113863 36244268
     [Google Scholar]
  18. PascutD. PratamaM.Y. VoN.V.T. MasadahR. TiribelliC. The crosstalk between tumor cells and the microenvironment in hepatocellular carcinoma: The role of exosomal microRNAs and their clinical implications.Cancer202012482310.3390/cancers12040823 32235370
     [Google Scholar]
  19. HegdeM. KumarA. GirisaS. Exosomal noncoding RNA-mediated spatiotemporal regulation of lipid metabolism: Implications in immune evasion and chronic inflammation.Cytokine Growth Factor Rev.20237311413410.1016/j.cytogfr.2023.06.001 37419767
     [Google Scholar]
  20. HuangS. NishiumiS. AsaduzzamanM. Exosome-derived small non-coding RNAs reveal immune response upon grafting transplantation in Pinctada fucata (Mollusca).Open Biol.202212521031710.1098/rsob.210317 35506205
     [Google Scholar]
  21. PaolilloM. SchinelliS. Integrins and exosomes, a dangerous liaison in cancer progression.Cancers2017989510.3390/cancers9080095 28933725
     [Google Scholar]
  22. HayashiY. MakinoT. SatoE. Density and maturity of peritumoral tertiary lymphoid structures in oesophageal squamous cell carcinoma predicts patient survival and response to immune checkpoint inhibitors.Br. J. Cancer2023128122175218510.1038/s41416‑023‑02235‑9 37016103
     [Google Scholar]
  23. OkudaS. OhuchidaK. NakamuraS. Neoadjuvant chemotherapy enhances anti-tumor immune response of tumor microenvironment in human esophageal squamous cell carcinoma.iScience202326410648010.1016/j.isci.2023.106480 37091252
     [Google Scholar]
  24. MezheyeuskiA. BackmanM. MattssonJ. An immune score reflecting pro- and anti-tumoural balance of tumour microenvironment has major prognostic impact and predicts immunotherapy response in solid cancers.EBioMedicine20238810445210.1016/j.ebiom.2023.104452 36724681
     [Google Scholar]
  25. ZhangZ.F. A novel pyroptosis scoring model was associated with the prognosis and immune microenvironment of esophageal squamous cell carcinoma.Front. Genet.202313103460610.3389/fgene.2022.1034606 36685978
     [Google Scholar]
  26. YuanH. QingT. ZhuS. The effects of altered DNA damage repair genes on mutational processes and immune cell infiltration in esophageal squamous cell carcinoma.Cancer Med.2023128100771009010.1002/cam4.5663 36708047
     [Google Scholar]
  27. ZhaoZ. YangS. ZhouA. Small extracellular vesicles in the development, diagnosis, and possible therapeutic application of esophageal squamous cell carcinoma.Front. Oncol.20211173270210.3389/fonc.2021.732702 34527593
     [Google Scholar]
  28. ZengH. GuoS. RenX. WuZ. LiuS. YaoX. Current strategies for exosome cargo loading and targeting delivery.Cells20231210141610.3390/cells12101416 37408250
     [Google Scholar]
  29. BinangH.B. PereraC.J. ApteM.V. Role of pancreatic tumour-derived exosomes and their cargo in pancreatic cancer-related diabetes.Int. J. Mol. Sci.202324121020310.3390/ijms241210203 37373351
     [Google Scholar]
  30. VahabiM. ComandatoreA. FranczakM.A. Role of exosomes in transferring chemoresistance through modulation of cancer glycolytic cell metabolism.Cytokine Growth Factor Rev.20237316317210.1016/j.cytogfr.2023.07.004 37541790
     [Google Scholar]
  31. LvY. DuX. TangW. YangQ. GaoF. Exosomes: The role in tumor tolerance and the potential strategy for tumor therapy.Pharmaceutics202315246210.3390/pharmaceutics15020462 36839784
     [Google Scholar]
  32. LudwigN. YerneniS.S. HarasymczukM. TGFβ carrying exosomes in plasma: Potential biomarkers of cancer progression in patients with head and neck squamous cell carcinoma.Br. J. Cancer202312891733174110.1038/s41416‑023‑02184‑3 36810911
     [Google Scholar]
  33. WeberB. SturmR. HenrichD. Diagnostic and prognostic potential of exosomal cytokines IL-6 and IL-10 in polytrauma patients.Int. J. Mol. Sci.202324141183010.3390/ijms241411830 37511589
     [Google Scholar]
  34. ChenX. LiY. LiM. Exosomal miRNAs assist in the crosstalk between tumor cells and immune cells and its potential therapeutics.Life Sci.202332912193410.1016/j.lfs.2023.121934 37460057
     [Google Scholar]
  35. HongF. LiN. FengZ. ZhengY. ZhuC. ZhangF. Exosomal microRNAs as novel diagnostic biomarkers in breast cancer: A systematic evaluation and meta-analysis.Asian J. Surg.202346114727473610.1016/j.asjsur.2023.05.115 37301624
     [Google Scholar]
  36. ShokatiE. SafariE. The immunomodulatory role of exosomal microRNA networks in the crosstalk between tumor-associated myeloid-derived suppressor cells and tumor cells.Int. Immunopharmacol.202312011026710.1016/j.intimp.2023.110267 37276829
     [Google Scholar]
  37. BianD. WuY. SongG. AziziR. ZamaniA. The application of mesenchymal stromal cells (MSCs) and their derivative exosome in skin wound healing: A comprehensive review.Stem Cell Res. Ther.20221312410.1186/s13287‑021‑02697‑9 35073970
     [Google Scholar]
  38. OlejarzW. Kubiak-TomaszewskaG. ChrzanowskaA. LorencT. Exosomes in angiogenesis and anti-angiogenic therapy in cancers.Int. J. Mol. Sci.20202116584010.3390/ijms21165840 32823989
     [Google Scholar]
  39. WangS. LiF. YeT. Macrophage-tumor chimeric exosomes accumulate in lymph node and tumor to activate the immune response and the tumor microenvironment.Sci. Transl. Med.202113615eabb698110.1126/scitranslmed.abb6981 34644149
     [Google Scholar]
  40. MorishitaM. TakahashiY. MatsumotoA. NishikawaM. TakakuraY. Exosome-based tumor antigens–adjuvant co-delivery utilizing genetically engineered tumor cell-derived exosomes with immunostimulatory CpG DNA.Biomaterials2016111556510.1016/j.biomaterials.2016.09.031 27723556
     [Google Scholar]
  41. Labani-MotlaghA. NaseriS. WentheJ. ErikssonE. LoskogA. Systemic immunity upon local oncolytic virotherapy armed with immunostimulatory genes may be supported by tumor-derived exosomes.Mol. Ther. Oncolytics20212050851810.1016/j.omto.2021.02.007 33738337
     [Google Scholar]
  42. YaoY. ChenL. WeiW. DengX. MaL. HaoS. Tumor cell-derived exosome-targeted dendritic cells stimulate stronger CD8+ CTL responses and antitumor immunities.Biochem. Biophys. Res. Commun.20134361606510.1016/j.bbrc.2013.05.058 23707941
     [Google Scholar]
  43. HuW. HuangF. NingL. HaoJ. WanJ. HaoS. Enhanced immunogenicity of leukemia-derived exosomes via transfection with lentiviral vectors encoding costimulatory molecules.Cell. Oncol.202043588990010.1007/s13402‑020‑00535‑3 32578140
     [Google Scholar]
  44. ChenG. HuangA.C. ZhangW. Exosomal PD-L1 contributes to immunosuppression and is associated with anti-PD-1 response.Nature2018560771838238610.1038/s41586‑018‑0392‑8 30089911
     [Google Scholar]
  45. MorrisseyS.M. YanJ. Exosomal PD-L1: Roles in tumor progression and immunotherapy.Trends Cancer20206755055810.1016/j.trecan.2020.03.002 32610067
     [Google Scholar]
  46. PoggioM. HuT. PaiC.C. Suppression of exosomal PD-L1 induces systemic anti-tumor immunity and memory.Cell20191772414427.e1310.1016/j.cell.2019.02.016 30951669
     [Google Scholar]
  47. XieF. XuM. LuJ. MaoL. WangS. The role of exosomal PD-L1 in tumor progression and immunotherapy.Mol. Cancer201918114610.1186/s12943‑019‑1074‑3 31647023
     [Google Scholar]
  48. MorrisseyS.M. ZhangF. DingC. Tumor-derived exosomes drive immunosuppressive macrophages in a pre-metastatic niche through glycolytic dominant metabolic reprogramming.Cell Metab.2021331020402058.e1010.1016/j.cmet.2021.09.002 34559989
     [Google Scholar]
  49. XieQ.H. ZhengJ.Q. DingJ.Y. Exosome-mediated immunosuppression in tumor microenvironments.Cells20221112194610.3390/cells11121946 35741075
     [Google Scholar]
  50. JiaoY. ZhangT. LiuM. Exosomal PGE2 from M2 macrophages inhibits neutrophil recruitment and NET formation through lipid mediator class switching in sepsis.J. Biomed. Sci.20233016210.1186/s12929‑023‑00957‑9 37533081
     [Google Scholar]
  51. XieX. YangX. WuJ. Exosome from indoleamine 2,3-dioxygenase-overexpressing bone marrow mesenchymal stem cells accelerates repair process of ischemia/reperfusion-induced acute kidney injury by regulating macrophages polarization.Stem Cell Res. Ther.202213136710.1186/s13287‑022‑03075‑9 35902956
     [Google Scholar]
  52. ZhangJ. LiS. LiL. Exosome and exosomal microRNA: Trafficking, sorting, and function.Genomics Proteomics Bioinformatics2015131172410.1016/j.gpb.2015.02.001 25724326
     [Google Scholar]
  53. SunZ. ShiK. YangS. Effect of exosomal miRNA on cancer biology and clinical applications.Mol. Cancer201817114710.1186/s12943‑018‑0897‑7 30309355
     [Google Scholar]
  54. TiongT.Y. ChanM. WangC.H. Exosomal miR-21 determines lung-to-brain metastasis specificity through the DGKB/ERK axis within the tumor microenvironment.Life Sci.202332912194510.1016/j.lfs.2023.121945 37454756
     [Google Scholar]
  55. ShaoY. LiY. JiangY. LiH. WangJ. ZhangD. Circulating exosomal miR ‐155‐5p contributes to severe acute pancreatitis‐associated intestinal barrier injury by targeting SOCS1 to activate NLRP3 inflammasome‐mediated pyroptosis.FASEB J.2023376e2300310.1096/fj.202300237R 37219532
     [Google Scholar]
  56. WangD. WangX. SongY. Exosomal miR-146a-5p and miR-155-5p promote CXCL12/CXCR7-induced metastasis of colorectal cancer by crosstalk with cancer-associated fibroblasts.Cell Death Dis.202213438010.1038/s41419‑022‑04825‑6 35443745
     [Google Scholar]
  57. LiuK. DouR. YangC. Exosome-transmitted miR-29a induces colorectal cancer metastasis by destroying the vascular endothelial barrier.Carcinogenesis202344435636710.1093/carcin/bgad013 36939367
     [Google Scholar]
  58. ChenS. MaoY. ChenW. Serum exosomal miR-34a as a potential biomarker for the diagnosis and prognostic of hepatocellular carcinoma.J. Cancer20221351410141710.7150/jca.57205 35371309
     [Google Scholar]
  59. DiW. ZhangW. ZhuB. LiX. TangQ. ZhouY. Colorectal cancer prompted adipose tissue browning and cancer cachexia through transferring exosomal miR‐146b‐5p.J. Cell. Physiol.202123675399541010.1002/jcp.30245 33368224
     [Google Scholar]
  60. PetanidisS. DomvriK. PorpodisK. Inhibition of kras-derived exosomes downregulates immunosuppressive BACH2/GATA-3 expression via RIP-3 dependent necroptosis and miR-146/miR-210 modulation.Biomed. Pharmacother.202012210946110.1016/j.biopha.2019.109461 31918262
     [Google Scholar]
  61. ZhouJ. LiX. WuX. Exosomes released from tumor-associated macrophages transfer miRNAs that induce a Treg/Th17 cell imbalance in epithelial ovarian cancer.Cancer Immunol. Res.20186121578159210.1158/2326‑6066.CIR‑17‑0479 30396909
     [Google Scholar]
  62. JinY. MengQ. ZhangB. Cancer-associated fibroblasts-derived exosomal miR-3656 promotes the development and progression of esophageal squamous cell carcinoma via the ACAP2/PI3K-AKT signaling pathway.Int. J. Biol. Sci.202117143689370110.7150/ijbs.62571 34671193
     [Google Scholar]
  63. ZhangY. ChenC. LiuZ. PABPC1-induced stabilization of IFI27 mRNA promotes angiogenesis and malignant progression in esophageal squamous cell carcinoma through exosomal miRNA-21-5p.J. Exp. Clin. Cancer Res.202241111110.1186/s13046‑022‑02339‑9 35346324
     [Google Scholar]
  64. LiW. ZhangL. GuoB. Exosomal FMR1-AS1 facilitates maintaining cancer stem-like cell dynamic equilibrium via TLR7/NFκB/c-Myc signaling in female esophageal carcinoma.Mol. Cancer20191812210.1186/s12943‑019‑0949‑7 30736860
     [Google Scholar]
  65. WangZ ZhangM LiuL Prognostic and immunological role of cancer-associated fibroblasts-derived exosomal protein in esophageal squamous cell carcinoma.Int Immunopharmacol2023124Pt A11083710.1016/j.intimp.2023.110837
     [Google Scholar]
  66. WangH. QiY. LanZ. Exosomal PD-L1 confers chemoresistance and promotes tumorigenic properties in esophageal cancer cells via upregulating STAT3/miR-21.Gene Ther.2023301-28810010.1038/s41434‑022‑00331‑8 35440807
     [Google Scholar]
  67. ZhangY. BiJ. HuangJ. TangY. DuS. LiP. Exosome: A review of its classification, isolation techniques, storage, diagnostic and targeted therapy applications.Int. J. Nanomedicine2020156917693410.2147/IJN.S264498 33061359
     [Google Scholar]
  68. ZhangL. YuD. Exosomes in cancer development, metastasis, and immunity.Biochim. Biophys. Acta Rev. Cancer20191871245546810.1016/j.bbcan.2019.04.004 31047959
     [Google Scholar]
  69. WangX. ZhouY. DingK. Roles of exosomes in cancer chemotherapy resistance, progression, metastasis and immunity, and their clinical applications (Review).Int. J. Oncol.20215914410.3892/ijo.2021.5224 34013358
     [Google Scholar]
  70. XiongJ. ChiH. YangG. Revolutionizing anti-tumor therapy: Unleashing the potential of B cell-derived exosomes.Front. Immunol.202314118876010.3389/fimmu.2023.1188760 37342327
     [Google Scholar]
  71. CuiB. SunJ. LiS.P. CD80+ dendritic cell derived exosomes inhibit CD8+ T cells through down-regulating NLRP3 expression after liver transplantation.Int. Immunopharmacol.202210910878710.1016/j.intimp.2022.108787 35490667
     [Google Scholar]
  72. GhorbaninezhadF. AlemohammadH. NajafzadehB. Dendritic cell-derived exosomes: A new horizon in personalized cancer immunotherapy?Cancer Lett.202356221616810.1016/j.canlet.2023.216168 37031915
     [Google Scholar]
  73. LiD. ZhouX. XuW. Prostate cancer cells synergistically defend against CD8+ T cells by secreting exosomal PD‐L1.Cancer Med.20231215164051641510.1002/cam4.6275 37501397
     [Google Scholar]
  74. YongT. ZhangX. BieN. Tumor exosome-based nanoparticles are efficient drug carriers for chemotherapy.Nat. Commun.2019101383810.1038/s41467‑019‑11718‑4 31444335
     [Google Scholar]
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Exosome-Derived Cargos in Immune Microenvironment in Esophageal Carcinoma: A Mini-Review
Recent Patents on Anti-Cancer Drug Discovery 20, 137 (2025); https://doi.org/10.2174/0115748928280161231123060159
/content/journals/pra/10.2174/0115748928280161231123060159
/content/journals/pra/10.2174/0115748928280161231123060159
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  • Article Type:     Review Article
Keyword(s): cargos; esophageal carcinoma; Exosomes; immune microenvironment; immune response; targets

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