肿瘤源性外泌体在头颈鳞状细胞癌微环境中的免疫调节作用

doi:10.6040/j.issn.1673-3770.0.2022.541

Abstract

Abstract: Head and neck squamous cell carcinoma is one of the most common malignancies. Tumor-derived exosomes can participate in immune cell regulation through direct interaction with cell receptors or fusion with plasma membrane in immune cells, which plays animportant role in the regulation of head and neck squamous cell carcinoma. Tumor-derived exosomes can not only inhibit the effects of killing immune cells on tumors, but also negatively regulate immunosuppressive cell response to promote immune escape of tumor cells, and thus regulate the process of tumorigenesis, development, and distant metastases. This review summarizes the latest research on tumor-derived exosome functions in regulating different types of immune cells in the microenvironment of head and neck squamous cell carcinoma. Through the exploration of tumor-derived exosome regulation of the tumor microenvironment, we aim to realize new strategies of exosome drug delivery and tumor targeted therapy.

Key words: Head and neck squamous cell carcinoma, Tumor-derived exosomes, Killing immune cell, Inhibitory immune cells, Tumor microenvironment

CLC Number:

R762

SONG Fei, SONG Hao, LI Yumei, MOU Yakui, SONG Xicheng. Immunomodulatory roles of tumor-derived exosomes in the microenvironment of head and neck squamous cell carcinoma[J].Journal of Otolaryngology and Ophthalmology of Shandong University, 2024, 38(1): 92-100.

References

[1] Johnson DE, Burtness B, Leemans CR, et al. Head and neck squamous cell carcinoma[J]. Nat Rev Dis Primers, 2020, 6(1): 92. doi:10.1038/s41572-020-00224-3
[2] Sun Z, Sun XD, Chen ZW, et al. Head and neck squamous cell carcinoma: risk factors, molecular alterations, immunology and peptide vaccines[J]. Int J Pept Res Ther, 2022, 28(1): 19. doi:10.1007/s10989-021-10334-5
[3] Yang DB, Zhang WH, Zhang HY, et al. Progress, opportunity, and perspective on exosome isolation-efforts for efficient exosome-based theranostics[J]. Theranostics, 2020, 10(8): 3684-3707. doi:10.7150/thno.41580
[4] Li Y, Gao ST, Hu Q, et al. Functional properties of cancer epithelium and stroma-derived exosomes in head and neck squamous cell carcinoma[J]. Life(Basel), 2022, 12(5): 757. doi:10.3390/life12050757
[5] Shao JT, Zaro J, Shen YX. Advances in exosome-based drug delivery and tumor targeting: from tissue distribution to intracellular fate[J]. Int J Nanomedicine, 2020, 15: 9355-9371. doi:10.2147/IJN.S281890
[6] Mashouri L, Yousefi H, Aref AR, et al. Exosomes: composition, biogenesis, and mechanisms in cancer metastasis and drug resistance[J]. Mol Cancer, 2019, 18(1): 75. doi:10.1186/s12943-019-0991-5
[7] Dai J, Su YZ, Zhong SY, et al. Exosomes: key players in cancer and potential therapeutic strategy[J]. Signal Transduct Target Ther, 2020, 5(1): 145. doi:10.1038/s41392-020-00261-0
[8] Li BW, Cao Y, Sun MJ, et al. Expression, regulation, and function of exosome-derived miRNAs in cancer progression and therapy[J]. FASEB J, 2021, 35(10): e21916. doi:10.1096/fj.202100294RR
[9] Wang HB, Lu ZM, Zhao XX. Tumorigenesis, diagnosis, and therapeutic potential of exosomes in liver cancer[J]. J Hematol Oncol, 2019, 12(1): 133. doi:10.1186/s13045-019-0806-6
[10] Jing Z, Chen K, Gong L. The significance of exosomes in pathogenesis, diagnosis, and treatment of esophageal cancer[J]. Int J Nanomed, 2021, 16: 6115-6127. doi:10.2147/IJN.S321555
[11] Jin MZ, Jin WL. The updated landscape of tumor microenvironment and drug repurposing[J]. Signal Transduct Target Ther, 2020, 5(1): 166. doi:10.1038/s41392-020-00280-x
[12] Khalaf K, Hana D, Chou JT, et al. Aspects of the tumor microenvironment involved in immune resistance and drug resistance[J]. Front Immunol, 2021, 12: 656364. doi:10.3389/fimmu.2021.656364
[13] Wieckowski EU, Visus C, Szajnik M, et al. Tumor-derived microvesicles promote regulatory T cell expansion and induce apoptosis in tumor-reactive activated CD8⁺ T lymphocytes[J]. J Immunol, 2009, 183(6): 3720-3730. doi:10.4049/jimmunol.0900970
[14] Rheinländer A, Schraven B, Bommhardt U. CD45 in human physiology and clinical medicine[J]. Immunol Lett, 2018, 196: 22-32. doi:10.1016/j.imlet.2018.01.009
[15] Beccard IJ, Hofmann L, Schroeder JC, et al. Immune suppressive effects of plasma-derived exosome populations in head and neck cancer[J]. Cancers(Basel), 2020, 12(7): 1997. doi:10.3390/cancers12071997
[16] Razzo BM, Ludwig N, Hong CS, et al. Tumor-derived exosomes promote carcinogenesis of murine oral squamous cell carcinoma[J]. Carcinogenesis, 2020, 41(5): 625-633. doi:10.1093/carcin/bgz124
[17] Kim JW, Wieckowski E, Taylor DD, et al. Fas ligand-positive membranous vesicles isolated from sera of patients with oral cancer induce apoptosis of activated T lymphocytes[J]. Clin Cancer Res, 2005, 11(3): 1010-1020
[18] Theodoraki MN, Yerneni SS, Hoffmann TK, et al. Clinical significance of PD-L1⁺ exosomes in plasma of head and neck cancer patients[J]. Clin Cancer Res, 2018, 24(4): 896-905. doi:10.1158/1078-0432.CCR-17-2664
[19] Gao Q, Liu HT, Xu YQ, et al. Serum-derived exosomes promote CD8⁺ T cells to overexpress PD-1, affecting the prognosis of hypopharyngeal carcinoma[J]. Cancer Cell Int, 2021, 21(1): 584. doi:10.1186/s12935-021-02294-z
[20] Maybruck BT, Pfannenstiel LW, Diaz-Montero M, et al. Tumor-derived exosomes induce CD8⁺ T cell suppressors[J]. J Immunother Cancer, 2017, 5(1): 65. doi:10.1186/s40425-017-0269-7
[21] Masucci MT, Minopoli M, Carriero MV. Tumor associated neutrophils. their role in tumorigenesis, metastasis, prognosis and therapy[J]. Front Oncol, 2019, 9: 1146. doi:10.3389/fonc.2019.01146
[22] Takenaka Y, Oya R, Kitamiura T, et al. Prognostic role of neutrophil-to-lymphocyte ratio in head and neck cancer: a meta-analysis[J]. Head Neck, 2018, 40(3): 647-655. doi:10.1002/hed.24986
[23] Schuldner M, Dörsam B, Shatnyeva O, et al. Exosome-dependent immune surveillance at the metastatic niche requires BAG6 and CBP/p300-dependent acetylation of p53[J]. Theranostics, 2019, 9(21): 6047-6062. doi:10.7150/thno.36378
[24] Liu YD, Li CF, Lu YP, et al. Tumor microenvironment-mediated immune tolerance in development and treatment of gastric cancer[J]. Front Immunol, 2022, 13: 1016817. doi:10.3389/fimmu.2022.1016817
[25] Leal AC, Mizurini DM, Gomes T, et al. Tumor-derived exosomes induce the formation of neutrophil extracellular traps: implications for the establishment of cancer-associated thrombosis[J]. Sci Rep, 2017, 7(1): 6438. doi:10.1038/s41598-017-06893-7
[26] Zhang X, Shi H, Yuan X, et al. Tumor-derived exosomes induce N2 polarization of neutrophils to promote gastric cancer cell migration[J]. Mol Cancer, 2018, 17(1): 146. doi:10.1186/s12943-018-0898-6
[27] Tuo BJ, Chen Z, Dang Q, et al. Roles of exosomal circRNAs in tumour immunity and cancer progression[J]. Cell Death Dis, 2022, 13(6): 539. doi:10.1038/s41419-022-04949-9
[28] Shang AQ, Gu CZ, Wang WW, et al. Exosomal circPACRGL promotes progression of colorectal cancer via the miR-142-3p/miR-506-3p- TGF-β1 axis[J]. Mol Cancer, 2020, 19(1): 117. doi:10.1186/s12943-020-01235-0
[29] Yang M, Shurin GV, Zhu PY, et al. Dendritic cells in the cancer microenvironment[J]. J Cancer, 2013, 4(1): 36-44. doi:10.7150/jca.5046
[30] Cheng PY, Corzo CA, Luetteke N, et al. Inhibition of dendritic cell differentiation and accumulation of myeloid-derived suppressor cells in cancer is regulated by S100A9 protein[J]. J Exp Med, 2008, 205(10): 2235-2249. doi:10.1084/jem.20080132
[31] Farren MR, Carlson LM, Netherby CS, et al. Tumor-induced STAT3 signaling in myeloid cells impairs dendritic cell generation by decreasing PKCβII abundance[J]. Sci Signal, 2014, 7(313): ra16. doi:10.1126/scisignal.2004656
[32] Lopatina T, Sarcinella A, Brizzi MF. Tumour derived extracellular vesicles: challenging target to blunt tumour immune evasion[J]. Cancers, 2022, 14(16): 4020. doi:10.3390/cancers14164020
[33] Maus RLG, Jakub JW, Hieken TJ, et al. Identification of novel, immune-mediating extracellular vesicles in human lymphatic effluent draining primary cutaneous melanoma[J]. Oncoimmunology, 2019, 8(12): e1667742. doi:10.1080/2162402X.2019.1667742
[34] Mittal SK, Roche PA. Suppression of antigen presentation by IL-10[J]. Curr Opin Immunol, 2015, 34: 22-27. doi:10.1016/j.coi.2014.12.009
[35] Wang YZ, Yi J, Chen XG, et al. The regulation of cancer cell migration by lung cancer cell-derived exosomes through TGF-β and IL-10[J]. Oncol Lett, 2016, 11(2): 1527-1530. doi:10.3892/ol.2015.4044
[36] Sim WJ, Ahl PJ, Connolly JE. Metabolism is central to tolerogenic dendritic cell function[J]. Mediators Inflamm, 2016: 2636701. doi:10.1155/2016/2636701
[37] Yin XZ, Zeng WF, Wu BW, et al. PPARα inhibition overcomes tumor-derived exosomal lipid-induced dendritic cell dysfunction[J]. Cell Rep, 2020, 33(3): 108278. doi:10.1016/j.celrep.2020.108278
[38] Zong JB, Keskinov AA, Shurin GV, et al. Tumor-derived factors modulating dendritic cell function[J]. Cancer Immunol Immunother, 2016, 65(7): 821-833. doi:10.1007/s00262-016-1820-y
[39] Gottfried E, Kunz-Schughart LA, Ebner S, et al. Tumor-derived lactic acid modulates dendritic cell activation and antigen expression[J]. Blood, 2006, 107(5): 2013-2021. doi:10.1182/blood-2005-05-1795
[40] Hosseini R, Asef-Kabiri L, Yousefi H, et al. The roles of tumor-derived exosomes in altered differentiation, maturation and function of dendritic cells[J]. Mol Cancer, 2021, 20(1): 83. doi:10.1186/s12943-021-01376-w
[41] Salimu J, Webber J, Gurney M, et al. Dominant immunosuppression of dendritic cell function by prostate-cancer-derived exosomes[J]. J Extracell Vesicles, 2017, 6(1): 1368823. doi:10.1080/20013078.2017.1368823
[42] Wu CP, Wang M, Huang Q, et al. Aberrant expression profiles and bioinformatic analysis of CAF-derived exosomal miRNAs from three moderately differentiated supraglottic LSCC patients[J]. J Clin Lab Anal, 2022, 36(1): e24108. doi:10.1002/jcla.24108
[43] Allard B, Longhi MS, Robson SC, et al. The ectonucleotidases CD39 and CD73: novel checkpoint inhibitor targets[J]. Immunol Rev, 2017, 276(1): 121-144. doi:10.1111/imr.12528
[44] Sun YY, Guo MF, Feng YJ, et al. Effect of ginseng polysaccharides on NK cell cytotoxicity in immunosuppressed mice[J]. Exp Ther Med, 2016, 12(6): 3773-3777. doi:10.3892/etm.2016.3840
[45] Liu CR, Yu SH, Zinn K, et al. Murine mammary carcinoma exosomes promote tumor growth by suppression of NK cell function[J]. J Immunol, 2006, 176(3): 1375-1385. doi:10.4049/jimmunol.176.3.1375
[46] Hong CS, Sharma P, Yerneni SS, et al. Circulating exosomes carrying an immunosuppressive cargo interfere with cellular immunotherapy in acute myeloid leukemia[J]. Sci Rep, 2017, 7(1): 14684. doi:10.1038/s41598-017-14661-w
[47] Berchem G, Noman MZ, Bosseler M, et al. Hypoxic tumor-derived microvesicles negatively regulate NK cell function by a mechanism involving TGF-β and miR23a transfer[J]. Oncoimmunology, 2016, 5(4): e1062968. doi:10.1080/2162402X.2015.1062968
[48] Park EJ, Myint PK, Appiah MG, et al. Ligand-competent fractalkine receptor is expressed on exosomes[J]. Biochem Biophys Rep, 2021, 26: 100932. doi:10.1016/j.bbrep.2021.100932
[49] Wang YN, Qin X, Zhu XQ, et al. Oral cancer-derived exosomal NAP1 enhances cytotoxicity of natural killer cells via the IRF-3 pathway[J]. Oral Oncol, 2018, 76: 34-41. doi:10.1016/j.oraloncology.2017.11.024
[50] Li Q, Huang QP, Huyan T, et al. Bifacial effects of engineering tumour cell-derived exosomes on human natural killer cells[J]. Exp Cell Res, 2018, 363(2): 141-150. doi:10.1016/j.yexcr.2017.12.005
[51] Zhu XQ, Qin X, Wang XN, et al. Oral cancer cellderived exosomes modulate natural killer cell activity by regulating the receptors on these cells[J]. Int J Mol Med, 2020, 46(6): 2115-2125. doi:10.3892/ijmm.2020.4736
[52] Ludwig S, Floros T, Theodoraki MN, et al. Suppression of lymphocyte functions by plasma exosomes correlates with disease activity in patients with head and neck cancer[J]. Clin Cancer Res, 2017, 23(16): 4843-4854. doi:10.1158/1078-0432.CCR-16-2819
[53] Hosseini R, Sarvnaz H, Arabpour M, et al. Cancer exosomes and natural killer cells dysfunction: biological roles, clinical significance and implications for immunotherapy[J]. Mol Cancer, 2022, 21(1): 15. doi:10.1186/s12943-021-01492-7
[54] Dysthe M, Parihar R. Myeloid-derived suppressor cells in the tumor microenvironment[J]. Adv Exp Med Biol, 2020, 1224: 117-140. doi:10.1007/978-3-030-35723-8_8
[55] Chalmin F, Ladoire S, Mignot G, et al. Membrane-associated Hsp72 from tumor-derived exosomes mediates STAT3-dependent immunosuppressive function of mouse and human myeloid-derived suppressor cells[J]. J Clin Invest, 2010, 120(2): 457-471. doi:10.1172/JCI40483
[56] Vasquez-Dunddel D, Pan F, Zeng Q, et al. STAT3 regulates arginase-I in myeloid-derived suppressor cells from cancer patients[J]. J Clin Invest, 2013, 123(4): 1580-1589. doi:10.1172/JCI60083
[57] Shiah SG, Chou ST, Chang JY. microRNAs: their role in metabolism, tumor microenvironment, and therapeutic implications in head and neck squamous cell carcinoma[J]. Cancers, 2021, 13(22): 5604. doi:10.3390/cancers13225604
[58] Guo XF, Qiu W, Wang J, et al. Glioma exosomes mediate the expansion and function of myeloid-derived suppressor cells through microRNA-29a/Hbp1 and microRNA-92a/Prkar1a pathways[J]. Int J Cancer, 2019, 144(12): 3111-3126. doi:10.1002/ijc.32052
[59] Kamigaki T, Ibe H, Okada S, et al. Improvement of impaired immunological status of patients with various types of advanced cancers by autologous immune cell therapy[J]. Anticancer Res, 2015, 35(8): 4535-4543
[60] Chen WZ, Jiang JX, Xia WJ, et al. Tumor-related exosomes contribute to tumor-promoting microenvironment: an immunological perspective[J]. J Immunol Res, 2017, 2017: 1073947. doi:10.1155/2017/1073947
[61] Muller L, Simms P, Hong CS, et al. Human tumor-derived exosomes(TEX)regulate Treg functions via cell surface signaling rather than uptake mechanisms[J]. Oncoimmunology, 2017, 6(8): e1261243. doi:10.1080/2162402X.2016.1261243
[62] Ning T, Li JL, He Y, et al. Exosomal miR-208b related with oxaliplatin resistance promotes Treg expansion in colorectal cancer[J]. Mol Ther, 2021, 29(9): 2723-2736. doi:10.1016/j.ymthe.2021.04.028
[63] Szajnik M, Czystowska M, Szczepanski MJ, et al. Tumor-derived microvesicles induce, expand and up-regulate biological activities of human regulatory T cells(Treg)[J]. PLoS One, 2010, 5(7): e11469. doi:10.1371/journal.pone.0011469
[64] Reale A, Khong T, Spencer A. Extracellular vesicles and their roles in the tumor immune microenvironment[J]. J Clin Med, 2022, 11(23): 6892. doi:10.3390/jcm11236892
[65] Liu ZX, Rui T, Lin ZY, et al. Tumor-associated macrophages promote metastasis of oral squamous cell carcinoma via CCL13 regulated by stress granule[J]. Cancers(Basel), 2022, 14(20): 5081. doi:10.3390/cancers14205081
[66] Cai JH, Qiao B, Gao N, et al. Oral squamous cell carcinoma-derived exosomes promote M2 subtype macrophage polarization mediated by exosome-enclosed miR-29a-3p[J]. Am J Physiol Cell Physiol, 2019, 316(5): C731-C740. doi:10.1152/ajpcell.00366.2018
[67] Hsieh CH, Tai SK, Yang MH. Snail-overexpressing cancer cells promote M2-like polarization of tumor-associated macrophages by delivering miR-21-abundant exosomes[J]. Neoplasia, 2018, 20(8): 775-788. doi:10.1016/j.neo.2018.06.004
[68] Yuan Y, Jiao PF, Wang ZY, et al. Endoplasmic reticulum stress promotes the release of exosomal PD-L1 from head and neck cancer cells and facilitates M2 macrophage polarization[J]. Cell Commun Signal, 2022, 20(1): 12. doi:10.1186/s12964-021-00810-2
[69] Bellmunt àM, López-Puerto L, Lorente J, et al. Involvement of extracellular vesicles in the macrophage-tumor cell communication in head and neck squamous cell carcinoma[J]. PLoS One, 2019, 14(11): e0224710. doi:10.1371/journal.pone.0224710
[70] Pang X, Wang SS, Zhang M, et al. OSCC cell-secreted exosomal CMTM6 induced M2-like macrophages polarization via ERK1/2 signaling pathway[J]. Cancer Immunol Immunother, 2021, 70(4): 1015-1029. doi:10.1007/s00262-020-02741-2
[71] Zhou Y, Que KT, Zhang Z, et al. Iron overloaded polarizes macrophage to proinflammation phenotype through ROS/acetyl-p53 pathway[J]. Cancer Med, 2018, 7(8): 4012-4022. doi:10.1002/cam4.1670
[72] Soh J, Lim ZX, Lim EH, et al. Ironing out exercise on immuno-oncological outcomes[J]. J Immunother Cancer, 2022, 10(9): e002976. doi:10.1136/jitc-2021-002976
[73] Chen WH, Zuo F, Zhang KW, et al. Exosomal MIF derived from nasopharyngeal carcinoma promotes metastasis by repressing ferroptosis of macrophages[J]. Front Cell Dev Biol, 2021, 9: 791187. doi:10.3389/fcell.2021.791187
[74] 边晓敏, 韩光红. 细胞外囊泡在头颈部肿瘤中的研究进展[J]. 山东大学耳鼻喉眼学报, 2020, 34(1): 99-104. doi: 10.6040/j.issn.1673-3770.0.2019.370 BIAN Xiaomin, HAN Guanghong. Recent advances regarding extracellular vesicles in head and neck cancers[J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2020, 34(1): 99-104. doi: 10.6040/j.issn.1673-3770.0.2019.370
[75] Yu D, Li Y, Wang M, et al. Exosomes as a new frontier of cancer liquid biopsy[J]. Mol Cancer. 2022, 21(1): 56. doi: 10.1186/s12943-022-01509-9
[76] Zhang L, Yu DH. Exosomes in cancer development, metastasis, and immunity[J]. Biochim Biophys Acta Rev Cancer, 2019, 1871(2): 455-468. doi:10.1016/j.bbcan.2019.04.004
[77] Pathania AS, Prathipati P, Challagundla KB. New insights into exosome mediated tumor-immune escape: clinical perspectives and therapeutic strategies[J]. Biochim Biophys Acta BBA Rev Cancer, 2021, 1876(2): 188624. doi:10.1016/j.bbcan.2021.188624
[78] Kim SM, Yang Y, Oh SJ, et al. Cancer-derived exosomes as a delivery platform of CRISPR/Cas9 confer cancer cell tropism-dependent targeting[J]. J Control Release, 2017, 266: 8-16. doi:10.1016/j.jconrel.2017.09.013
[79] Yong TY, Zhang XQ, Bie NN, et al. Tumor exosome-based nanoparticles are efficient drug carriers for chemotherapy[J]. Nat Commun, 2019, 10(1): 3838. doi:10.1038/s41467-019-11718-4
[80] 张旭平, 刘雪霞. 外泌体在变态反应性疾病中的研究进展[J]. 山东大学耳鼻喉眼学报, 2021, 35(2): 136-140. doi:10.6040/j.issn.1673-3770.0.2020.285 ZHANG Xuping, LIU Xuexia. Current progress of exosome research in allergic diseases[J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2021, 35(2): 136-140. doi:10.6040/j.issn.1673-3770.0.2020.285
[81] Hu SC, Ma JH, Su C, et al. Engineered exosome-like nanovesicles suppress tumor growth by reprogramming tumor microenvironment and promoting tumor ferroptosis[J]. Acta Biomater, 2021, 135: 567-581. doi:10.1016/j.actbio.2021.09.003

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Immunomodulatory roles of tumor-derived exosomes in the microenvironment of head and neck squamous cell carcinoma

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