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Exosome-mediated crosstalk between tumor cells and innate immune cells: implications for cancer progression and therapeutic strategies

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Abstract

The increasing number of cancer-associated deaths despite the substantial improvement in diagnosis and treatment has sparked discussions on the need for novel biomarkers and therapeutic strategies for cancer. Exosomes have become crucial players in tumor development and progression, largely due to the diverse nature of their cargo content released to recipient cells. Importantly, exosome-mediated crosstalk between tumor and stromal cells is essential in reprogramming the tumor microenvironment to facilitate tumor progression. As a result, exosomes have gradually become a marker for the early diagnosis of many diseases and an important tool in drug delivery systems. However, the precise mechanisms by which exosomes participate in tumor progression remain elusive, multifaceted, and a double-edged sword, thus requiring further clarification. The available evidence suggests that exosomes can facilitate communication between innate immune cells and tumor cells to either support or inhibit tumor progression. Herein, this review focused on exosome-mediated intercellular communication between tumor cells and macrophages, neutrophils, mast cells, monocytes, dendritic cells, and natural killer cells. Specifically, how such intercellular communication affects tumor progression has been described. It has also been discussed that, depending on their cargo, exosomes can suppress or promote tumor cell progression. In addition, the potential application of exosomes and strategies to target exosomes in cancer treatment has been comprehensively discussed.

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References

  • Ahmad S, Srivastava RK, Singh P, Naik UP, Srivastava AK (2022) Role of extracellular vesicles in glia-neuron intercellular communication. Front Mole Neurosci. https://doi.org/10.3389/fnmol.2022.844194

    Article  Google Scholar 

  • Alkhateeb AA, Connor JR (1836) 2013 The significance of ferritin in cancer: Anti-oxidation, inflammation and tumorigenesis. Biochimica Et Biophys Acta (BBA) Rev Cancer 1836(2):245–254

    Google Scholar 

  • Bahrami A, Khazaei M, Hassanian SM, ShahidSales S, Joudi-Mashhad M, Maftouh M et al (2018) Targeting the tumor microenvironment as a potential therapeutic approach in colorectal cancer: rational and progress. J Cell Physiol 233(4):2928–2936

    CAS  PubMed  Google Scholar 

  • Banerjee S, Halder K, Ghosh S, Bose A, Majumdar S (2015) The combination of a novel immunomodulator with a regulatory T cell suppressing antibody (DTA-1) regress advanced stage B16F10 solid tumor by repolarizing tumor associated macrophages in situ. Oncoimmunology 4(3):e995559

    PubMed  PubMed Central  Google Scholar 

  • Bejarano L, Jordāo MJC, Joyce JA (2021) Therapeutic targeting of the tumor microenvironment. Cancer Discov 11(4):933–959

    CAS  PubMed  Google Scholar 

  • Binenbaum Y, Fridman E, Yaari Z, Milman N, Schroeder A, Ben David G et al (2018) Transfer of miRNA in macrophage-derived exosomes induces drug resistance in pancreatic adenocarcinoma. Can Res 78(18):5287–5299

    CAS  Google Scholar 

  • Bray F, Laversanne M, Weiderpass E, Soerjomataram I (2021) The ever-increasing importance of cancer as a leading cause of premature death worldwide. Cancer 127(16):3029–3030

    PubMed  Google Scholar 

  • Cai Z, Zhang M, Boafo Kwantwi L, Bi X, Zhang C, Cheng Z et al (2020) Breast cancer cells promote self-migration by secreting interleukin 8 to induce NET formation. Gene 754:144902

    CAS  PubMed  Google Scholar 

  • Chaudhary A, Bag S, Arora N, Radhakrishnan VS, Mishra D, Mukherjee G (2022) Hypoxic transformation of immune cell metabolism within the microenvironment of oral cancers. Front Oral Health. https://doi.org/10.3389/froh.2020.585710

    Article  Google Scholar 

  • Chen X, Zhou J, Li X, Wang X, Lin Y, Wang X (2018a) Exosomes derived from hypoxic epithelial ovarian cancer cells deliver microRNAs to macrophages and elicit a tumor-promoted phenotype. Cancer Lett 435:80–91

    CAS  PubMed  Google Scholar 

  • Chen S, Lv M, Fang S, Ye W, Gao Y, Xu Y (2018b) Poly(I:C) enhanced anti-cervical cancer immunities induced by dendritic cells-derived exosomes. Int J Biol Macromol 113:1182–1187

    CAS  PubMed  Google Scholar 

  • Chen Q, Li Y, Gao W, Chen L, Xu W, Zhu X (2021) Exosome-mediated crosstalk between tumor and tumor-associated macrophages. Front Mole Biosci. https://doi.org/10.3389/fmolb.2021.764222

    Article  Google Scholar 

  • Chen J, Lin Z, Liu L, Zhang R, Geng Y, Fan M et al (2021a) GOLM1 exacerbates CD8+ T cell suppression in hepatocellular carcinoma by promoting exosomal PD-L1 transport into tumor-associated macrophages. Signal Transduct Target Ther 6(1):397

    CAS  PubMed  PubMed Central  Google Scholar 

  • Chen J, Zhang K, Zhi Y, Wu Y, Chen B, Bai J et al (2021b) Tumor-derived exosomal miR-19b-3p facilitates M2 macrophage polarization and exosomal LINC00273 secretion to promote lung adenocarcinoma metastasis via Hippo pathway. Clin Transl Med 11(9):e478

    CAS  PubMed  PubMed Central  Google Scholar 

  • Chen S, Chen Z, Li Z, Li S, Wen Z, Cao L et al (2022) Tumor-associated macrophages promote cholangiocarcinoma progression via exosomal Circ_0020256. Cell Death Dis 13(1):94

    CAS  PubMed  PubMed Central  Google Scholar 

  • Cheng L, Wang Y, Huang L (2017) Exosomes from M1-polarized macrophages potentiate the cancer vaccine by creating a pro-inflammatory microenvironment in the lymph node. Mole Therapy J Am Soc Gene Therapy 25(7):1665–1675

    CAS  Google Scholar 

  • Cheng Z, Wang L, Wu C, Huang L, Ruan Y, Xue W (2021) Tumor-derived exosomes induced M2 macrophage polarization and promoted the metastasis of osteosarcoma cells through tim-3. Arch Med Res 52(2):200–210

    CAS  PubMed  Google Scholar 

  • Choo YW, Kang M, Kim HY, Han J, Kang S, Lee JR et al (2018) M1 macrophage-derived nanovesicles potentiate the anticancer efficacy of immune checkpoint inhibitors. ACS Nano 12(9):8977–8993

    CAS  PubMed  Google Scholar 

  • Cowman SJ, Fuja DG, Liu X-D, Tidwell RSS, Kandula N, Sirohi D et al (2020) Macrophage HIF-1α is an independent prognostic indicator in kidney cancer. Clin Cancer Res 26(18):4970–4982

    CAS  PubMed  PubMed Central  Google Scholar 

  • Cui Z, Li W, Wang Y, Zhao M, Liu K, Yang Y et al (2022) M2 macrophage-derived exosomal ferritin heavy chain promotes colon cancer cell proliferation. Biolog Trace Element Res. https://doi.org/10.1007/s12011-022-03488-w

    Article  Google Scholar 

  • Di Pace AL, Tumino N, Besi F, Alicata C, Conti LA, Munari E et al (2020) Characterization of human NK Cell-derived exosomes: role of DNAM1 receptor in exosome-mediated cytotoxicity against tumor. Cancers (basel) 12(3):661

    PubMed  Google Scholar 

  • Diamond JM, Vanpouille-Box C, Spada S, Rudqvist NP, Chapman JR, Ueberheide BM et al (2018) Exosomes Shuttle TREX1-Sensitive IFN-Stimulatory dsDNA from Irradiated Cancer Cells to DCs. Cancer Immunol Res 6(8):910–920

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ding G, Zhou L, Qian Y, Fu M, Chen J, Chen J et al (2015) Pancreatic cancer-derived exosomes transfer miRNAs to dendritic cells and inhibit RFXAP expression via miR-212-3p. Oncotarget 6(30):29877–29888

    PubMed  PubMed Central  Google Scholar 

  • Dominiak A, Chełstowska B, Olejarz W, Nowicka G (2020) Communication in the cancer microenvironment as a target for therapeutic interventions. Cancers 12(5):1232

    CAS  PubMed  PubMed Central  Google Scholar 

  • Du S, Qian J, Tan S, Li W, Liu P, Zhao J et al (2022) Tumor cell-derived exosomes deliver TIE2 protein to macrophages to promote angiogenesis in cervical cancer. Cancer Lett 529:168–179

    CAS  PubMed  Google Scholar 

  • El-Arabey AA, Denizli M, Kanlikilicer P, Bayraktar R, Ivan C, Rashed M et al (2020) GATA3 as a master regulator for interactions of tumor-associated macrophages with high-grade serous ovarian carcinoma. Cell Signal 68:109539

    CAS  PubMed  Google Scholar 

  • Fu X-H, Li J-P, Li X-Y, Tan Y, Zhao M, Zhang S-F et al (2022) M2-macrophage-derived exosomes promote meningioma progression through TGF-<i>β</i> signaling pathway. J Immunol Res 2022:8326591

    PubMed  PubMed Central  Google Scholar 

  • Gabrusiewicz K, Li X, Wei J, Hashimoto Y, Marisetty AL, Ott M et al (2018) Glioblastoma stem cell-derived exosomes induce M2 macrophages and PD-L1 expression on human monocytes. Oncoimmunology 7(4):e1412909

    PubMed  PubMed Central  Google Scholar 

  • Gastpar R, Gehrmann M, Bausero MA, Asea A, Gross C, Schroeder JA et al (2005) Heat shock protein 70 surface-positive tumor exosomes stimulate migratory and cytolytic activity of natural killer cells. Can Res 65(12):5238–5247

    CAS  Google Scholar 

  • Gunassekaran GR, Poongkavithai Vadevoo SM, Baek MC, Lee B (2021) M1 macrophage exosomes engineered to foster M1 polarization and target the IL-4 receptor inhibit tumor growth by reprogramming tumor-associated macrophages into M1-like macrophages. Biomaterials 278:121137

    CAS  PubMed  Google Scholar 

  • Haderk F, Schulz R, Iskar M, Cid LL, Worst T, Willmund KV et al (2017) Tumor-derived exosomes modulate PD-L1 expression in monocytes. Sci Immunol 2(13):eaah5509

    PubMed  Google Scholar 

  • Han D, Wang K, Zhang T, Gao GC, Xu H (2020) Natural killer cell-derived exosome-entrapped paclitaxel can enhance its anti-tumor effect. Eur Rev Med Pharmacol Sci 24(10):5703–5713

    CAS  PubMed  Google Scholar 

  • Han C, Zhang C, Wang H, Zhao L (2021) Exosome-mediated communication between tumor cells and tumor-associated macrophages: implications for tumor microenvironment. Oncoimmunology 10(1):1887552

    PubMed  PubMed Central  Google Scholar 

  • Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144(5):646–674

    CAS  PubMed  Google Scholar 

  • Hao S, Yuan J, Xiang J (2007) Nonspecific CD4(+) T cells with uptake of antigen-specific dendritic cell-released exosomes stimulate antigen-specific CD8(+) CTL responses and long-term T cell memory. J Leukoc Biol 82(4):829–838

    CAS  PubMed  Google Scholar 

  • He C, Zheng S, Luo Y, Wang B (2018) Exosome theranostics: biology and translational medicine. Theranostics 8(1):237–255

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hsieh C-H, Tai S-K, Yang M-H (2018) Snail-overexpressing cancer cells promote M2-like polarization of tumor-associated macrophages by delivering MiR-21-abundant exosomes. Neoplasia 20(8):775–788

    CAS  PubMed  PubMed Central  Google Scholar 

  • Huang L, Wang F, Wang X, Su C, Wu S, Yang C et al (2023) M2-like macrophage-derived exosomes facilitate metastasis in non-small-cell lung cancer by delivering integrin αVβ3. MedComm 4(1):e191

    CAS  PubMed  Google Scholar 

  • Hwang WL, Lan HY, Cheng WC, Huang SC, Yang MH (2019) Tumor stem-like cell-derived exosomal RNAs prime neutrophils for facilitating tumorigenesis of colon cancer. J Hematol Oncol 12(1):10

    PubMed  PubMed Central  Google Scholar 

  • Jang JY, Lee JK, Jeon YK, Kim CW (2013) Exosome derived from epigallocatechin gallate treated breast cancer cells suppresses tumor growth by inhibiting tumor-associated macrophage infiltration and M2 polarization. BMC Cancer 13:421

    PubMed  PubMed Central  Google Scholar 

  • Javeed N, Gustafson MP, Dutta SK, Lin Y, Bamlet WR, Oberg AL et al (2017) Immunosuppressive CD14(+)HLA-DR(lo/neg) monocytes are elevated in pancreatic cancer and “primed” by tumor-derived exosomes. Oncoimmunology 6(1):e1252013

    PubMed  Google Scholar 

  • Jella KK, Nasti TH, Li Z, Lawson DH, Switchenko JM, Ahmed R et al (2020) Exosome-containing preparations from postirradiated mouse melanoma cells delay melanoma growth in vivo by a natural killer cell-dependent mechanism. Int J Radiat Oncol Biol Phys 108(1):104–114

    PubMed  PubMed Central  Google Scholar 

  • Jiang Z, Zhang Y, Zhang Y, Jia Z, Zhang Z, Yang J (2021a) Cancer derived exosomes induce macrophages immunosuppressive polarization to promote bladder cancer progression. Cell Commun Signal 19(1):93

    CAS  PubMed  PubMed Central  Google Scholar 

  • Jiang Y, Jiang H, Wang K, Liu C, Man X, Fu Q (2021b) Hypoxia enhances the production and antitumor effect of exosomes derived from natural killer cells. Ann Trans Med 9(6):473

    CAS  Google Scholar 

  • Kaban K, Hinterleitner C, Zhou Y, Salva E, Kantarci AG, Salih HR et al (2021) Therapeutic silencing of BCL-2 using NK cell-derived exosomes as a novel therapeutic approach in breast cancer. Cancers (basel) 13(10):2397

    CAS  PubMed  Google Scholar 

  • Kahlert C, Kalluri R (2013) Exosomes in tumor microenvironment influence cancer progression and metastasis. J Mol Med (berl) 91(4):431–437

    CAS  PubMed  Google Scholar 

  • Kamerkar S, Leng C, Burenkova O, Jang SC, McCoy C, Zhang K et al (2022) Exosome-mediated genetic reprogramming of tumor-associated macrophages by exoASO-STAT6 leads to potent monotherapy antitumor activity. Sci Advan 8(7):7002

    Google Scholar 

  • Kim H, Park H-J, Chang HW, Back JH, Lee SJ, Park YE et al (2022) Exosome-guided direct reprogramming of tumor-associated macrophages from protumorigenic to antitumorigenic to fight cancer. Bioact Mater 25:527–540

    PubMed  PubMed Central  Google Scholar 

  • Kitai Y, Kawasaki T, Sueyoshi T, Kobiyama K, Ishii KJ, Zou J et al (2017) DNA-containing exosomes derived from cancer cells treated with topotecan activate a STING-dependent pathway and reinforce antitumor immunity. J Immunol 198(4):1649–1659

    CAS  PubMed  Google Scholar 

  • Kong W, Zhang L, Chen Y, Yu Z, Zhao Z (2022) Cancer cell-derived exosomal LINC00313 induces M2 macrophage differentiation in non-small cell lung cancer. Clin Transl Oncol 24(12):2395–2408

    CAS  PubMed  Google Scholar 

  • Kwantwi LB (2023a) Interplay between tumor-derived factors and tumor-associated neutrophils: opportunities for therapeutic interventions in cancer. Clin Trans Oncol off Pub Federat Span Oncol Soc Nat Cancer Instit Mexico. https://doi.org/10.1007/s12094-023-03100-0

    Article  Google Scholar 

  • Kwantwi LB (2023b) Overcoming anti-PD-1/PD-L1 immune checkpoint blockade resistance: the role of macrophage, neutrophils and mast cells in the tumor microenvironment. Clin Exp Med. https://doi.org/10.1007/s10238-023-01059-4

    Article  PubMed  Google Scholar 

  • Kwantwi LB, Wang S, Sheng Y, Wu Q (2021) Multifaceted roles of CCL20 (C-C motif chemokine ligand 20): mechanisms and communication networks in breast cancer progression. Bioengineered 12(1):6923–6934

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lambert JD, Hong J, Yang GY, Liao J, Yang CS (2005) Inhibition of carcinogenesis by polyphenols: evidence from laboratory investigations. Am J Clin Nutr 81(1 Suppl):284s-s291

    CAS  PubMed  Google Scholar 

  • Lan J, Sun L, Xu F, Liu L, Hu F, Song D et al (2019) M2 macrophage-derived exosomes promote cell migration and invasion in colon cancer. Can Res 79(1):146–158

    CAS  Google Scholar 

  • Leal AC, Mizurini DM, Gomes T, Rochael NC, Saraiva EM, Dias MS et al (2017) Tumor-derived exosomes induce the formation of neutrophil extracellular traps: implications for the establishment of cancer-associated thrombosis. Sci Rep 7(1):6438

    PubMed  PubMed Central  Google Scholar 

  • Li X, Tang M (2020) Exosomes released from M2 macrophages transfer miR-221-3p contributed to EOC progression through targeting CDKN1B. Cancer Med 9(16):5976–5988

    CAS  PubMed  PubMed Central  Google Scholar 

  • Li X, Lei Y, Wu M, Li N (2018) Regulation of macrophage activation and polarization by HCC-derived exosomal lncRNA TUC339. Int J Mol Sci 19(10):2958

    PubMed  PubMed Central  Google Scholar 

  • Li B, Song T-N, Wang F-R, Yin C, Li Z, Lin J-P et al (2019) Tumor-derived exosomal HMGB1 promotes esophageal squamous cell carcinoma progression through inducing PD1+ TAM expansion. Oncogenesis 8(3):17

    CAS  PubMed  PubMed Central  Google Scholar 

  • Li Z, Suo B, Long G, Gao Y, Song J, Zhang M et al (2020a) Exosomal miRNA-16-5p derived from M1 macrophages enhances T cell-dependent immune response by regulating PD-L1 in gastric cancer. Front Cell Develop Biol 8:572689

    Google Scholar 

  • Li M, Fang L, Kwantwi LB, He G, Luo W, Yang L et al (2021) N-Myc promotes angiogenesis and therapeutic resistance of prostate cancer by TEM8. Med Oncol 38(10):127

    CAS  PubMed  PubMed Central  Google Scholar 

  • Li M, Xu H, Qi Y, Pan Z, Li B, Gao Z et al (2022a) Tumor-derived exosomes deliver the tumor suppressor miR-3591-3p to induce M2 macrophage polarization and promote glioma progression. Oncogene 41(41):4618–4632

    CAS  PubMed  PubMed Central  Google Scholar 

  • Li J, Li N, Wang J (2020b) M1 macrophage-derived exosome-encapsulated cisplatin can enhance its anti-lung cancer effect. Minerva Medica. https://doi.org/10.23736/S0026-4806.20.06564-7

  • Li H, Zeng C, Shu C, Cao Y, Shao W, Zhang M et al (2022b) Laminins in tumor-derived exosomes upregulated by ETS1 reprogram omental macrophages to promote omental metastasis of ovarian cancer. Cell Death Dis 13(12):1028

    CAS  PubMed  PubMed Central  Google Scholar 

  • Liang ZX, Liu HS, Wang FW, Xiong L, Zhou C, Hu T et al (2019) LncRNA RPPH1 promotes colorectal cancer metastasis by interacting with TUBB3 and by promoting exosomes-mediated macrophage M2 polarization. Cell Death Dis 10(11):829

    PubMed  PubMed Central  Google Scholar 

  • Liang Y, Duan L, Lu J, Xia J (2021) Engineering exosomes for targeted drug delivery. Theranostics 11(7):3183–3195

    CAS  PubMed  PubMed Central  Google Scholar 

  • Liu C, Yu S, Zinn K, Wang J, Zhang L, Jia Y et al (2006) Murine mammary carcinoma exosomes promote tumor growth by suppression of NK cell function. J Immunol 176(3):1375–1385

    CAS  PubMed  Google Scholar 

  • Liu Y, Gu Y, Cao X (2015) The exosomes in tumor immunity. Oncoimmunology 4(9):e1027472

    PubMed  PubMed Central  Google Scholar 

  • Liu Y, Gu Y, Han Y, Zhang Q, Jiang Z, Zhang X et al (2016) Tumor exosomal RNAs promote lung pre-metastatic niche formation by activating alveolar epithelial TLR3 to recruit neutrophils. Cancer Cell 30(2):243–256

    PubMed  Google Scholar 

  • Liu J, Fan L, Yu H, Zhang J, He Y, Feng D et al (2019) Endoplasmic reticulum stress causes liver cancer cells to release exosomal miR-23a-3p and up-regulate programmed death ligand 1 expression in macrophages. Hepatology 70(1):241–258

    CAS  PubMed  Google Scholar 

  • Liu J, Wu S, Zheng X, Zheng P, Fu Y, Wu C et al (2020) Immune suppressed tumor microenvironment by exosomes derived from gastric cancer cells via modulating immune functions. Sci Rep 10(1):14749

    CAS  PubMed  PubMed Central  Google Scholar 

  • Liu W, Long Q, Zhang W, Zeng D, Hu B, Liu S et al (2021) miRNA-221-3p derived from M2-polarized tumor-associated macrophage exosomes aggravates the growth and metastasis of osteosarcoma through SOCS3/JAK2/STAT3 axis. Aging 13(15):19760–19775

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ludwig N, Yerneni SS, Azambuja JH, Gillespie DG, Menshikova EV, Jackson EK et al (2020) Tumor-derived exosomes promote angiogenesis via adenosine A(2B) receptor signaling. Angiogenesis 23(4):599–610

    CAS  PubMed  PubMed Central  Google Scholar 

  • Luo C, Xin H, Zhou Z, Hu Z, Sun R, Yao N et al (2022) Tumor-derived exosomes induce immunosuppressive macrophages to foster intrahepatic cholangiocarcinoma progression. Hepatology 76(4):982–999

    CAS  PubMed  Google Scholar 

  • Ma YS, Wu TM, Ling CC, Yu F, Zhang J, Cao PS et al (2021) M2 macrophage-derived exosomal microRNA-155-5p promotes the immune escape of colon cancer by downregulating ZC3H12B. Mole Therapy Oncolytics 20:484–498

    CAS  Google Scholar 

  • Maacha S, Bhat AA, Jimenez L, Raza A, Haris M, Uddin S et al (2019) Extracellular vesicles-mediated intercellular communication: roles in the tumor microenvironment and anti-cancer drug resistance. Mol Cancer 18(1):55

    PubMed  PubMed Central  Google Scholar 

  • Marciscano AE, Anandasabapathy N (2021) The role of dendritic cells in cancer and anti-tumor immunity. Semin Immunol 52:101481

    CAS  PubMed  PubMed Central  Google Scholar 

  • McAleese CE, Choudhury C, Butcher NJ, Minchin RF (2021) Hypoxia-mediated drug resistance in breast cancers. Cancer Lett 502:189–199

    CAS  PubMed  Google Scholar 

  • Meng W, Hao Y, He C, Li L, Zhu G (2019) Exosome-orchestrated hypoxic tumor microenvironment. Mol Cancer 18(1):57

    PubMed  PubMed Central  Google Scholar 

  • Mi X, Xu R, Hong S, Xu T, Zhang W, Liu M (2020) M2 macrophage-derived exosomal lncRNA AFAP1-AS1 and MicroRNA-26a affect cell migration and metastasis in esophageal cancer. Mole Therapy Nuc Acids 22:779–790

    CAS  Google Scholar 

  • Morrissey SM, Zhang F, Ding C, Montoya-Durango DE, Hu X, Yang C et al (2021) Tumor-derived exosomes drive immunosuppressive macrophages in a pre-metastatic niche through glycolytic dominant metabolic reprogramming. Cell Metab 33(10):2040–58.e10

    CAS  PubMed  PubMed Central  Google Scholar 

  • Mortezaee K, Majidpoor J (2021) The impact of hypoxia on immune state in cancer. Life Sci 286:120057

    CAS  PubMed  Google Scholar 

  • Morvan MG, Lanier LL (2016) NK cells and cancer: you can teach innate cells new tricks. Nat Rev Cancer 16(1):7–19

    CAS  PubMed  Google Scholar 

  • Munich S, Sobo-Vujanovic A, Buchser WJ, Beer-Stolz D, Vujanovic NL (2012) Dendritic cell exosomes directly kill tumor cells and activate natural killer cells via TNF superfamily ligands. Oncoimmunology 1(7):1074–1083

    PubMed  PubMed Central  Google Scholar 

  • Munir MT, Kay MK, Kang MH, Rahman MM, Al-Harrasi A, Choudhury M et al (2021) Tumor-associated macrophages as multifaceted regulators of breast tumor growth. Int J Mol Sci 22(12):6526

    CAS  PubMed  PubMed Central  Google Scholar 

  • Myers JA, Miller JS (2021) Exploring the NK cell platform for cancer immunotherapy. Nat Rev Clin Oncol 18(2):85–100

    PubMed  Google Scholar 

  • Näslund TI, Gehrmann U, Qazi KR, Karlsson MC, Gabrielsson S (2013) Dendritic cell-derived exosomes need to activate both T and B cells to induce antitumor immunity. J Immunol 190(6):2712–9

    PubMed  Google Scholar 

  • Neviani P, Wise PM, Murtadha M, Liu CW, Wu CH, Jong AY et al (2019) Natural killer-derived exosomal miR-186 inhibits neuroblastoma growth and immune escape mechanisms. Can Res 79(6):1151–1164

    CAS  Google Scholar 

  • Ning Y, Shen K, Wu Q, Sun X, Bai Y, Xie Y et al (2018) Tumor exosomes block dendritic cells maturation to decrease the T cell immune response. Immunol Lett 199:36–43

    CAS  PubMed  Google Scholar 

  • Ou B, Liu Y, Gao Z, Xu J, Yan Y, Li Y et al (2022) Senescent neutrophils-derived exosomal piRNA-17560 promotes chemoresistance and EMT of breast cancer via FTO-mediated m6A demethylation. Cell Death Dis 13(10):905

    CAS  PubMed  PubMed Central  Google Scholar 

  • Pegtel DM, Peferoen L, Amor S (2014) Extracellular vesicles as modulators of cell-to-cell communication in the healthy and diseased brain. Philosoph Trans Roy Soc B Biolog Sci 369(1652):20130516

    Google Scholar 

  • Pegtel DM, Gould SJ (2019) Exosomes. Annu Rev Biochem 88:487–514

    CAS  PubMed  Google Scholar 

  • Peng W, Sheng Y, Xiao H, Ye Y, Kwantwi LB, Cheng L et al (2022) Lung adenocarcinoma cells promote self-migration and self-invasion by activating neutrophils to upregulate notch3 expression of cancer cells. Front Mole Biosci. https://doi.org/10.3389/fmolb.2021.762729

    Article  Google Scholar 

  • Peng Y, Zhao M, Hu Y, Guo H, Zhang Y, Huang Y et al (2022) Blockade of exosome generation by GW4869 inhibits the education of M2 macrophages in prostate cancer. BMC Immunol 23(1):37

    CAS  PubMed  PubMed Central  Google Scholar 

  • Plebanek MP, Angeloni NL, Vinokour E, Li J, Henkin A, Martinez-Marin D et al (2017) Pre-metastatic cancer exosomes induce immune surveillance by patrolling monocytes at the metastatic niche. Nat Commun 8(1):1319

    PubMed  PubMed Central  Google Scholar 

  • Qian BZ, Li J, Zhang H, Kitamura T, Zhang J, Campion LR et al (2011) CCL2 recruits inflammatory monocytes to facilitate breast-tumour metastasis. Nature 475(7355):222–225

    CAS  PubMed  PubMed Central  Google Scholar 

  • Rajput AB, Turbin DA, Cheang MC, Voduc DK, Leung S, Gelmon KA et al (2008) Stromal mast cells in invasive breast cancer are a marker of favourable prognosis: a study of 4444 cases. Breast Cancer Res Treat 107(2):249–257

    PubMed  Google Scholar 

  • Rao X, Zhou X, Wang G, Jie X, Xing B, Xu Y et al (2022) NLRP6 is required for cancer-derived exosome-modified macrophage M2 polarization and promotes metastasis in small cell lung cancer. Cell Death Dis 13(10):891

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ratajczak MZ, Ratajczak J (2020) Extracellular microvesicles/exosomes: discovery, disbelief, acceptance, and the future? Leukemia 34(12):3126–3135

    PubMed  PubMed Central  Google Scholar 

  • Ribatti D, Ennas MG, Vacca A, Ferreli F, Nico B, Orru S et al (2003) Tumor vascularity and tryptase-positive mast cells correlate with a poor prognosis in melanoma. Eur J Clin Invest 33(5):420–425

    CAS  PubMed  Google Scholar 

  • Sato A, Rahman NIA, Shimizu A, Ogita H (2021) Cell-to-cell contact-mediated regulation of tumor behavior in the tumor microenvironment. Cancer Sci 112(10):4005–4012

    CAS  PubMed  PubMed Central  Google Scholar 

  • Schmitt CA, Wang B, Demaria M (2022) Senescence and cancer—role and therapeutic opportunities. Nat Rev Clin Oncol 19(10):619–636

    PubMed  PubMed Central  Google Scholar 

  • Shang A, Gu C, Zhou C, Yang Y, Chen C, Zeng B et al (2020) Exosomal KRAS mutation promotes the formation of tumor-associated neutrophil extracellular traps and causes deterioration of colorectal cancer by inducing IL-8 expression. Cell Commun Signal 18(1):52

    CAS  PubMed  PubMed Central  Google Scholar 

  • Shi C, Pamer EG (2011) Monocyte recruitment during infection and inflammation. Nat Rev Immunol 11(11):762–774

    CAS  PubMed  PubMed Central  Google Scholar 

  • Shobaki N, Sato Y, Suzuki Y, Okabe N, Harashima H (2020) Manipulating the function of tumor-associated macrophages by siRNA-loaded lipid nanoparticles for cancer immunotherapy. J Control Release 325:235–248

    CAS  PubMed  Google Scholar 

  • Shpyleva SI, Tryndyak VP, Kovalchuk O, Starlard-Davenport A, Chekhun VF, Beland FA et al (2011) Role of ferritin alterations in human breast cancer cells. Breast Cancer Res Treat 126(1):63–71

    CAS  PubMed  Google Scholar 

  • Song L, Luan B, Xu Q, Shi R, Wang X (2022) microRNA-155-3p delivered by M2 macrophages-derived exosomes enhances the progression of medulloblastoma through regulation of WDR82. J Transl Med 20(1):13

    CAS  PubMed  PubMed Central  Google Scholar 

  • Steitz AM, Steffes A, Finkernagel F, Unger A, Sommerfeld L, Jansen JM et al (2020) Tumor-associated macrophages promote ovarian cancer cell migration by secreting transforming growth factor beta induced (TGFBI) and tenascin C. Cell Death Dis 11(4):249

    CAS  PubMed  PubMed Central  Google Scholar 

  • Stuart EC, Scandlyn MJ, Rosengren RJ (2006) Role of epigallocatechin gallate (EGCG) in the treatment of breast and prostate cancer. Life Sci 79(25):2329–2336

    CAS  PubMed  Google Scholar 

  • Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A et al (2021) Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 Countries. CA Cancer J Clinic 71(3):209–49

    Google Scholar 

  • Travers M, Brown SM, Dunworth M, Holbert CE, Wiehagen KR, Bachman KE et al (2019) DFMO and 5-azacytidine increase M1 macrophages in the tumor microenvironment of murine ovarian cancer. Can Res 79(13):3445–3454

    CAS  Google Scholar 

  • Tyagi A, Wu SY, Sharma S, Wu K, Zhao D, Deshpande R et al (2022) Exosomal miR-4466 from nicotine-activated neutrophils promotes tumor cell stemness and metabolism in lung cancer metastasis. Oncogene 41(22):3079–3092

    CAS  PubMed  PubMed Central  Google Scholar 

  • van Niel G, D’Angelo G, Raposo G (2018) Shedding light on the cell biology of extracellular vesicles. Nat Rev Mol Cell Biol 19(4):213–228

    PubMed  Google Scholar 

  • Viaud S, Terme M, Flament C, Taieb J, André F, Novault S et al (2009) Dendritic cell-derived exosomes promote natural killer cell activation and proliferation: a role for NKG2D ligands and IL-15Ralpha. PLoS ONE 4(3):e4942

    PubMed  PubMed Central  Google Scholar 

  • Wan X, Xie B, Sun H, Gu W, Wang C, Deng Q et al (2022) Exosomes derived from M2 type tumor-associated macrophages promote osimertinib resistance in non-small cell lung cancer through MSTRG.292666.16-miR-6836–5p-MAPK8IP3 axis. Cancer Cell Int 22(1):83

    CAS  PubMed  PubMed Central  Google Scholar 

  • Wang X, Luo G, Zhang K, Cao J, Huang C, Jiang T et al (2018a) Hypoxic tumor-derived exosomal miR-301a mediates M2 macrophage polarization via PTEN/PI3Kγ to promote pancreatic cancer metastasis. Can Res 78(16):4586–4598

    CAS  Google Scholar 

  • Wang F, Li B, Wei Y, Zhao Y, Wang L, Zhang P et al (2018b) Tumor-derived exosomes induce PD1+ macrophage population in human gastric cancer that promotes disease progression. Oncogenesis 7(5):41

    PubMed  PubMed Central  Google Scholar 

  • Wang P, Wang H, Huang Q, Peng C, Yao L, Chen H et al (2019) Exosomes from M1-polarized macrophages enhance paclitaxel antitumor activity by activating macrophages-mediated inflammation. Theranostics 9(6):1714–1727

    CAS  PubMed  PubMed Central  Google Scholar 

  • Wang D, Wang X, Si M, Yang J, Sun S, Wu H et al (2020) Exosome-encapsulated miRNAs contribute to CXCL12/CXCR4-induced liver metastasis of colorectal cancer by enhancing M2 polarization of macrophages. Cancer Lett 474:36–52

    CAS  PubMed  Google Scholar 

  • Wang S, Li F, Ye T, Wang J, Lyu C, Qing S et al (2021) Macrophage-tumor chimeric exosomes accumulate in lymph node and tumor to activate the immune response and the tumor microenvironment. Sci Trans Med 13(615):eabb6981

    CAS  Google Scholar 

  • Wang Y, Shang K, Zhang N, Zhao J, Cao B (2021a) Tumor-associated macrophage-derived exosomes promote the progression of gastric cancer by regulating the P38MAPK signaling pathway and the immune checkpoint PD-L1. Cancer Biotherapy Radiopharm. https://doi.org/10.1089/cbr.2021.0218

    Article  Google Scholar 

  • Wang J, Tang W, Yang M, Yin Y, Li H, Hu F et al (2021b) Inflammatory tumor microenvironment responsive neutrophil exosomes-based drug delivery system for targeted glioma therapy. Biomaterials 273:120784

    CAS  PubMed  Google Scholar 

  • Whiteside TL (2016) Exosomes and tumor-mediated immune suppression. J Clin Investig 126(4):1216–1223

    PubMed  PubMed Central  Google Scholar 

  • Wu M, Wang G, Hu W, Yao Y, Yu XF (2019) Emerging roles and therapeutic value of exosomes in cancer metastasis. Mol Cancer 18(1):53

    PubMed  PubMed Central  Google Scholar 

  • Xiao H, Lässer C, Shelke GV, Wang J, Rådinger M, Lunavat TR et al (2014) Mast cell exosomes promote lung adenocarcinoma cell proliferation - role of KIT-stem cell factor signaling. Cell Commun Signal 12:64

    PubMed  PubMed Central  Google Scholar 

  • Xiao M, Zhang J, Chen W, Chen W (2018) M1-like tumor-associated macrophages activated by exosome-transferred THBS1 promote malignant migration in oral squamous cell carcinoma. J Exp Clin Cancer Res CR 37(1):143

    PubMed  Google Scholar 

  • Xiao H, He M, Xie G, Liu Y, Zhao Y, Ye X et al (2019) The release of tryptase from mast cells promote tumor cell metastasis via exosomes. BMC Cancer 19(1):1015

    PubMed  PubMed Central  Google Scholar 

  • Xing C, Li H, Li R-J, Yin L, Zhang H-F, Huang Z-N et al (2021) The roles of exosomal immune checkpoint proteins in tumors. Mil Med Res 8(1):56

    CAS  PubMed  PubMed Central  Google Scholar 

  • Xu K, Zhan Y, Yuan Z, Qiu Y, Wang H, Fan G et al (2019) Hypoxia induces drug resistance in colorectal cancer through the HIF-1α/miR-338-5p/IL-6 feedback loop. Mol Ther 27(10):1810–1824

    CAS  PubMed  PubMed Central  Google Scholar 

  • Xu Z, Zeng S, Gong Z, Yan Y (2020) Exosome-based immunotherapy: a promising approach for cancer treatment. Mol Cancer 19(1):160

    CAS  PubMed  PubMed Central  Google Scholar 

  • Xu M, Zhou C, Weng J, Chen Z, Zhou Q, Gao J et al (2022) Tumor associated macrophages-derived exosomes facilitate hepatocellular carcinoma malignance by transferring lncMMPA to tumor cells and activating glycolysis pathway. J Exp Clin Cancer Res CR 41(1):253

    CAS  PubMed  Google Scholar 

  • Yang F, Wang T, Du P, Fan H, Dong X, Guo H (2020) M2 bone marrow-derived macrophage-derived exosomes shuffle microRNA-21 to accelerate immune escape of glioma by modulating PEG3. Cancer Cell Int 20:93

    PubMed  PubMed Central  Google Scholar 

  • Yang Y, Guo Z, Chen W, Wang X, Cao M, Han X et al (2021) M2 macrophage-derived exosomes promote angiogenesis and growth of pancreatic ductal adenocarcinoma by targeting E2F2. Mole Therapy J Am Soc Gene Therapy 29(3):1226–1238

    CAS  Google Scholar 

  • Yasuda T, Baba H, Ishimoto T (2023) Cellular senescence in the tumor microenvironment and context-specific cancer treatment strategies. FEBS J 290(5):1290–302

    CAS  PubMed  Google Scholar 

  • Yin Z, Ma T, Huang B, Lin L, Zhou Y, Yan J et al (2019) Macrophage-derived exosomal microRNA-501-3p promotes progression of pancreatic ductal adenocarcinoma through the TGFBR3-mediated TGF-β signaling pathway. J Exp Clin Cancer Res CR 38(1):310

    PubMed  Google Scholar 

  • Yu S, Liu C, Su K, Wang J, Liu Y, Zhang L et al (2007) Tumor exosomes inhibit differentiation of bone marrow dendritic cells. J Immunol 178(11):6867–75

    CAS  PubMed  Google Scholar 

  • Yu C, Xue B, Li J, Zhang Q (2022) Tumor cell-derived exosome RNF126 affects the immune microenvironment and promotes nasopharyngeal carcinoma progression by regulating PTEN ubiquitination. Apoptosis 27(7):590–605

    CAS  PubMed  Google Scholar 

  • Yuan Y, Jiao P, Wang Z, Chen M, Du H, Xu L et al (2022) Endoplasmic reticulum stress promotes the release of exosomal PD-L1 from head and neck cancer cells and facilitates M2 macrophage polarization. Cell Commun Signal 20(1):12

    CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang X, Shi H, Yuan X, Jiang P, Qian H, Xu W (2018) Tumor-derived exosomes induce N2 polarization of neutrophils to promote gastric cancer cell migration. Mol Cancer 17(1):146

    PubMed  PubMed Central  Google Scholar 

  • Zhang P-F, Gao C, Huang X-Y, Lu J-C, Guo X-J, Shi G-M et al (2020) Cancer cell-derived exosomal circUHRF1 induces natural killer cell exhaustion and may cause resistance to anti-PD1 therapy in hepatocellular carcinoma. Mol Cancer 19(1):110

    CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang F, Sang Y, Chen D, Wu X, Wang X, Yang W et al (2021a) M2 macrophage-derived exosomal long non-coding RNA AGAP2-AS1 enhances radiotherapy immunity in lung cancer by reducing microRNA-296 and elevating NOTCH2. Cell Death Dis 12(5):467

    CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang S, Li D, Zhao M, Yang F, Sang C, Yan C et al (2021b) Exosomal miR-183-5p shuttled by M2 polarized tumor-associated macrophage promotes the development of colon cancer via targeting THEM4 mediated PI3K/AKT and NF-κB pathways. Front Oncol 11:672684

    CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang W, Zheng X, Yu Y, Zheng L, Lan J, Wu Y et al (2022) Renal cell carcinoma-derived exosomes deliver lncARSR to induce macrophage polarization and promote tumor progression via STAT3 pathway. Int J Biol Sci 18(8):3209–3222

    CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang J, Ji C, Zhang H, Shi H, Mao F, Qian H et al (2022) Engineered neutrophil-derived exosome-like vesicles for targeted cancer therapy. Sci Advan 8(2):8207

    Google Scholar 

  • Zhao S, Mi Y, Guan B, Zheng B, Wei P, Gu Y et al (2020) Tumor-derived exosomal miR-934 induces macrophage M2 polarization to promote liver metastasis of colorectal cancer. J Hematol Oncol 13(1):156

    PubMed  PubMed Central  Google Scholar 

  • Zhao Y, Liu L, Sun R, Cui G, Guo S, Han S et al (2022) Exosomes in cancer immunoediting and immunotherapy. Asian J Pharm Sci 17(2):193–205

    PubMed  PubMed Central  Google Scholar 

  • Zheng P, Chen L, Yuan X, Luo Q, Liu Y, Xie G et al (2017) Exosomal transfer of tumor-associated macrophage-derived miR-21 confers cisplatin resistance in gastric cancer cells. J Exp Clin Cancer Res 36(1):53

    PubMed  PubMed Central  Google Scholar 

  • Zheng P, Luo Q, Wang W, Li J, Wang T, Wang P et al (2018) Tumor-associated macrophages-derived exosomes promote the migration of gastric cancer cells by transfer of functional Apolipoprotein E. Cell Death Dis 9(4):434

    PubMed  PubMed Central  Google Scholar 

  • Zhou M, Chen J, Zhou L, Chen W, Ding G, Cao L (2014) Pancreatic cancer derived exosomes regulate the expression of TLR4 in dendritic cells via miR-203. Cell Immunol 292(1):65–69

    CAS  PubMed  Google Scholar 

  • Zhou J, Li X, Wu X, Zhang T, Zhu Q, Wang X et al (2018) Exosomes released from tumor-associated macrophages transfer miRNAs that induce a treg/Th17 cell imbalance in epithelial ovarian cancer. Cancer Immunol Res 6(12):1578–1592

    CAS  PubMed  Google Scholar 

  • Zhou S, Lan Y, Li Y, Li Z, Pu J, Wei L (2022) Hypoxic tumor-derived exosomes induce M2 macrophage polarization via PKM2/AMPK to promote lung cancer progression. Cell Trans 31:9636897221106998

    Google Scholar 

  • Zhu L, Kalimuthu S, Gangadaran P, Oh JM, Lee HW, Baek SH et al (2017) Exosomes derived from natural killer cells exert therapeutic effect in melanoma. Theranostics 7(10):2732–2745

    CAS  PubMed  PubMed Central  Google Scholar 

  • Zhu X, Shen H, Yin X, Yang M, Wei H, Chen Q et al (2019) Macrophages derived exosomes deliver miR-223 to epithelial ovarian cancer cells to elicit a chemoresistant phenotype. J Exp Clin Cancer Res CR 38(1):81

    PubMed  Google Scholar 

  • Zongqiang H, Jiapeng C, Yingpeng Z, Chuntao Y, Yiting W, Jiashun Z et al (2022) Exosomal miR-452-5p induce M2 macrophage polarization to accelerate hepatocellular carcinoma progression by targeting TIMP3. J Immunol Res 2022:1032106

    PubMed  PubMed Central  Google Scholar 

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Kwantwi, L.B. Exosome-mediated crosstalk between tumor cells and innate immune cells: implications for cancer progression and therapeutic strategies. J Cancer Res Clin Oncol 149, 9487–9503 (2023). https://doi.org/10.1007/s00432-023-04833-9

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