The link between intracellular calcium signaling and exosomal PD-L1 in cancer progression and immunotherapy

Md Rakibul Alam; Md Mizanur Rahman; Zhiguo Li

doi:10.1016/j.gendis.2023.01.026

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The link between intracellular calcium signaling and exosomal PD-L1 in cancer progression and immunotherapy

Review article | 更新时间：2024-02-04

- The link between intracellular calcium signaling and exosomal PD-L1 in cancer progression and immunotherapy
- Genes & Diseases Vol. 1, Issue 1, Pages: 321-334(2024)
- 作者机构：
  
  1. Department of Toxicology and Cancer Biology, College of Medicine, University of Kentucky,KY,Lexington,USA,40506
  2. Department of Medicine (Nephrology), Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta T6E2H7,Canada
- 作者简介：
- 基金信息：
- DOI：10.1016/j.gendis.2023.01.026
  CLC：
- Published：2024，
  
  Published Online：1 January 2024，
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Md Rakibul Alam, Md Mizanur Rahman, Zhiguo Li. The link between intracellular calcium signaling and exosomal PD-L1 in cancer progression and immunotherapy. [J]. Genes & Diseases 1(1):321-334(2024)
DOI：

Md Rakibul Alam, Md Mizanur Rahman, Zhiguo Li. The link between intracellular calcium signaling and exosomal PD-L1 in cancer progression and immunotherapy. [J]. Genes & Diseases 1(1):321-334(2024) DOI： 10.1016/j.gendis.2023.01.026.

摘要

Abstract

Exosomes are small membrane vesicles containing microRNA

RNA

DNA fragments

and proteins that are transferred from donor cells to recipient cells. Tumor cells release exosomes to reprogram the factors associated with the tumor microenvironment (TME) causing tumor metastasis and immune escape. Emerging evidence revealed that cancer cell-derived exosomes carry immune inhibitory molecule program death ligand 1 (PD-L1) that binds with receptor program death protein 1 (PD-1) and promote tumor progression by escaping immune response. Currently

some FDA-approved monoclonal antibodies are clinically used for cancer treatment by blocking PD-1/PD-L1 interaction. Despite notable treatment outcomes

some patients show poor drug response. Exosomal PD-L1 plays a vital role in lowering the treatment response

showing resistance to PD-1/PD-L1 blockage therapy through recapitulating the effect of cell surface PD-L1. To enhance therapeutic response

inhibition of exosomal PD-L1 is required. Calcium signaling is the central regulator of tumorigenesis and can regulate exosome biogenesis and secretion by modulating Rab GTPase family and membrane fusion factors. Immune checkpoints are also connected with calcium signaling and calcium channel blockers like amlodipine

nifedipine

lercanidipine

diltiazem

and verapamil were also reported to suppress cellular PD-L1 expression. Therefore

to enhance the PD-1/PD-L1 blockage therapy response

the reduction of exosomal PD-L1 secretion from cancer cells is in our therapeutic consideration. In this review

we proposed a therapeutic strategy by targeting calcium signaling to inhibit the expression of PD-L1-containing exosome levels that could reduce the anti-PD-1/PD-L1 therapy resistance and increase the patient's drug response rate.

关键词

Keywords

Calcium signalingCD8+T cellsExosomal PD-L1Exosomes biogenesisImmunosuppressionImmunotherapy

references

1 C. Théry, L. Zitvogel, S. AmigorenaExosomes: composition, biogenesis and function Nat Rev Immunol, 2 (8) (2002), pp. 569-579

2 S.E. Andaloussi, I. Mäger, X.O. Breakefield, et al.Extracellular vesicles: biology and emerging therapeutic opportunities Nat Rev Drug Discov, 12 (5) (2013), pp. 347-357

3 P.D. Robbins, A.E. MorelliRegulation of immune responses by extracellular vesicles Nat Rev Immunol, 14 (3) (2014), pp. 195-208

4 M.P. Plebanek, N.L. Angeloni, E. Vinokour, et al.Pre-metastatic cancer exosomes induce immune surveillance by patrolling monocytes at the metastatic niche Nat Commun, 8 (2017), p. 1319

5 K. Kimura, H. Hohjoh, M. Fukuoka, et al.Circulating exosomes suppress the induction of regulatory T cells via let-7i in multiple sclerosis Nat Commun, 9 (2018), p. 17

6 Y. Gui, H. Liu, L. Zhang, et al.Altered microRNA profiles in cerebrospinal fluid exosome in Parkinson disease and Alzheimer disease Oncotarget, 6 (35) (2015), pp. 37043-37053

7 G. Chen, A.C. Huang, W. Zhang, et al.Exosomal PD-L1 contributes to immunosuppression and is associated with anti-PD-1 response Nature, 560 (7718) (2018), pp. 382-386

8 F. Xie, M. Xu, J. Lu, et al.The role of exosomal PD-L1 in tumor progression and immunotherapy Mol Cancer, 18 (2019), p. 146

9 L. Shi, S. Chen, L. Yang, et al.The role of PD-1 and PD-L1 in T-cell immune suppression in patients with hematological malignancies J Hematol Oncol, 6 (2013), p. 74

10 L.M. Francisco, V.H. Salinas, K.E. Brown, et al.PD-L1 regulates the development, maintenance, and function of induced regulatory T cells J Exp Med, 206 (13) (2009), pp. 3015-3029

11 K. Bardhan, T. Anagnostou, V.A. BoussiotisThe PD1:PD-L1/2 pathway from discovery to clinical implementation Front Immunol, 7 (2016), p. 550

12 N. Kamimura, A.M. Wolf, Y. IwaiDevelopment of cancer immunotherapy targeting the PD-1 pathway J Nippon Med Sch, 86 (1) (2019), pp. 10-14

13 N. Patsoukis, J. Brown, V. Petkova, et al.Selective effects of PD-1 on Akt and Ras pathways regulate molecular components of the cell cycle and inhibit T cell proliferation Sci Signal, 5 (230) (2012), p. ra46

14 S.A. Zhang, H.E. Niyazi, W. Hong, et al.Effect of EBI3 on radiation-induced immunosuppression of cervical cancer HeLa cells by regulating Treg cells through PD-1/PD-L1 pathway Tumour Biol, 39 (3) (2017), Article 1010428317692237

15 N. Prevarskaya, R. Skryma, Y. ShubaCalcium in tumour metastasis: new roles for known actors Nat Rev Cancer, 11 (8) (2011), pp. 609-618

16 N. Déliot, B. ConstantinPlasma membrane calcium channels in cancer: alterations and consequences for cell proliferation and migration Biochim Biophys Acta, 1848 (10) (2015), pp. 2512-2522

17 M. Colombo, C. Moita, G. van Niel, et al.Analysis of ESCRT functions in exosome biogenesis, composition and secretion highlights the heterogeneity of extracellular vesicles J Cell Sci, 126 (Pt 24) (2013), pp. 5553-5565

18 C.E. Jackson, B.S. Scruggs, J.E. Schaffer, et al.Effects of inhibiting VPS4 support a general role for ESCRTs in extracellular vesicle biogenesis Biophys J, 113 (6) (2017), pp. 1342-1352

19 E.R. Abels, X.O. BreakefieldIntroduction to extracellular vesicles: biogenesis, RNA cargo selection, content, release, and uptake Cell Mol Neurobiol, 36 (3) (2016), pp. 301-312

20 J.P. Webber, L.K. Spary, A.J. Sanders, et al.Differentiation of tumour-promoting stromal myofibroblasts by cancer exosomes Oncogene, 34 (3) (2015), pp. 290-302

21 M. Ostrowski, N.B. Carmo, S. Krumeich, et al.Rab27a and Rab27b control different steps of the exosome secretion pathway Nat Cell Biol, 12 (1) (2010), pp. 19-30

22 A. Savina, M. Vidal, M.I. ColomboThe exosome pathway in K562 cells is regulated by Rab11 J Cell Sci, 115 (Pt 12) (2002), pp. 2505-2515

23 A. Savina, C.M. Fader, M.T. Damiani, et al.Rab11 promotes docking and fusion of multivesicular bodies in a calcium-dependent manner Traffic, 6 (2) (2005), pp. 131-143

24 G. Gorji-Bahri, H.R. Moghimi, A. HashemiRAB5A is associated with genes involved in exosome secretion: integration of bioinformatics analysis and experimental validation J Cell Biochem, 122 (3–4) (2021), pp. 425-441

25 D.J. Park, W.S. Yun, W.C. Kim, et al.Improvement of stem cell-derived exosome release efficiency by surface-modified nanoparticles J Nanobiotechnol, 18 (2020), p. 178

26 C. Hsu, Y. Morohashi, S.I. Yoshimura, et al.Regulation of exosome secretion by Rab35 and its GTPase-activating proteins TBC1D10A-C J Cell Biol, 189 (2) (2010), pp. 223-232

27 J.L. Johnson, J. He, M. Ramadass, et al.Munc13-4 is a Rab11-binding protein that regulates Rab11-positive vesicle trafficking and docking at the plasma membrane J Biol Chem, 291 (7) (2016), pp. 3423-3438

28 S.W. Messenger, S.S. Woo, Z. Sun, et al.A Ca2+-stimulated exosome release pathway in cancer cells is regulated by Munc13-4 J Cell Biol, 217 (8) (2018), pp. 2877-2890

29 S. Ariel, F. Marcelo, V. Michel, et al.Exosome release is regulated by a calcium-dependent mechanism in K562 cells J Biol Chem, 278 (22) (2003), pp. 20083-20090

30 A.L. Isola, S. ChenExosomes: the link between GPCR activation and metastatic potential? Front Genet, 7 (2016), p. 56

31 C. Kahlert, R. KalluriExosomes in tumor microenvironment influence cancer progression and metastasis J Mol Med, 91 (4) (2013), pp. 431-437

32 F. Chalmin, S. Ladoire, G. Mignot, et al.Membrane-associated Hsp72 from tumor-derived exosomes mediates STAT3-dependent immunosuppressive function of mouse and human myeloid-derived suppressor cells J Clin Invest, 120 (2) (2010), pp. 457-471

33 G. Jacquemet, H. Baghirov, M. Georgiadou, et al.L-type calcium channels regulate filopodia stability and cancer cell invasion downstream of integrin signalling Nat Commun, 7 (2016), p. 13297

34 W.M. Henne, H. Stenmark, S.D. EmrMolecular mechanisms of the membrane sculpting ESCRT pathway Cold Spring Harbor Perspect Biol, 5 (9) (2013), Article a016766

35 N.P. Hessvik, A. LlorenteCurrent knowledge on exosome biogenesis and release Cell Mol Life Sci, 75 (2) (2018), pp. 193-208

36 R. Mears, R.A. Craven, S. Hanrahan, et al.Proteomic analysis of melanoma-derived exosomes by two-dimensional polyacrylamide gel electrophoresis and mass spectrometry Proteomics, 4 (12) (2004), pp. 4019-4031

37 S. Runz, S. Keller, C. Rupp, et al.Malignant ascites-derived exosomes of ovarian carcinoma patients contain CD24 and EpCAM Gynecol Oncol, 107 (3) (2007), pp. 563-571

38 V. Ciravolo, V. Huber, G.C. Ghedini, et al.Potential role of HER2-overexpressing exosomes in countering trastuzumab-based therapy J Cell Physiol, 227 (2) (2012), pp. 658-667

39 I. Nazarenko, S. Rana, A. Baumann, et al.Cell surface tetraspanin Tspan8 contributes to molecular pathways of exosome-induced endothelial cell activation Cancer Res, 70 (4) (2010), pp. 1668-1678

40 M. Mathieu, L. Martin-Jaular, G. Lavieu, et al.Specificities of secretion and uptake of exosomes and other extracellular vesicles for cell-to-cell communication Nat Cell Biol, 21 (1) (2019), pp. 9-17

41 A.S. Jadli, N. Ballasy, P. Edalat, et al.Inside(sight) of tiny communicator: exosome biogenesis, secretion, and uptake Mol Cell Biochem, 467 (2020), pp. 77-94

42 B. Mansoori, A. Mohammadi, S. Davudian, et al.The different mechanisms of cancer drug resistance: a brief review Adv Pharmaceut Bull, 7 (3) (2017), pp. 339-348

43 M. Mostafazadeh, N. Samadi, H. Kahroba, et al.Potential roles and prognostic significance of exosomes in cancer drug resistance Cell Biosci, 11 (2021), p. 1

44 Q. Wu, Z. Yang, Y. Nie, et al.Multi-drug resistance in cancer chemotherapeutics: mechanisms and lab approaches Cancer Lett, 347 (2) (2014), pp. 159-166

45 Q. Wu, L. Zhou, D. Lv, et al.Exosome-mediated communication in the tumor microenvironment contributes to hepatocellular carcinoma development and progression J Hematol Oncol, 12 (2019), p. 53

46 I. Li, B.Y. NabetExosomes in the tumor microenvironment as mediators of cancer therapy resistance Mol Cancer, 18 (2019), p. 32

47 W. Song, D. Yan, T. Wei, et al.Tumor-derived extracellular vesicles in angiogenesis Biomed Pharmacother, 102 (2018), pp. 1203-1208

48 Y. Guo, X. Ji, J. Liu, et al.Effects of exosomes on pre-metastatic niche formation in tumors Mol Cancer, 18 (2019), p. 39

49 A. Schubert, M. BoutrosExtracellular vesicles and oncogenic signaling Mol Oncol, 15 (1) (2021), pp. 3-26

50 J. Liu, S. Wu, X. Zheng, et al.Immune suppressed tumor microenvironment by exosomes derived from gastric cancer cells via modulating immune functions Sci Rep, 10 (2020), p. 14749

51 F.G. Kugeratski, R. KalluriExosomes as mediators of immune regulation and immunotherapy in cancer FEBS J, 288 (1) (2021), pp. 10-35

52 J. Wada, H. Onishi, H. Suzuki, et al.Surface-bound TGF-beta1 on effusion-derived exosomes participates in maintenance of number and suppressive function of regulatory T-cells in malignant effusions Anticancer Res, 30 (9) (2010), pp. 3747-3757

53 L. Elsner, V. Muppala, M. Gehrmann, et al.The heat shock protein HSP70 promotes mouse NK cell activity against tumors that express inducible NKG2D ligands J Immunol, 179 (8) (2007), pp. 5523-5533

54 J. Wolfers, A. Lozier, G. Raposo, et al.Tumor-derived exosomes are a source of shared tumor rejection antigens for CTL cross-priming Nat Med, 7 (3) (2001), pp. 297-303

55 Z. Yin, M. Yu, T. Ma, et al.Mechanisms underlying low-clinical responses to PD-1/PD-L1 blocking antibodies in immunotherapy of cancer: a key role of exosomal PD-L1 J Immunother Cancer, 9 (1) (2021), Article e001698

56 M. Poggio, T. Hu, C.C. Pai, et al.Suppression of exosomal PD-L1 induces systemic anti-tumor immunity and memory Cell, 177 (2) (2019), pp. 414-427.e13

57 Y. Tang, P. Zhang, Y. Wang, et al.The biogenesis, biology, and clinical significance of exosomal PD-L1 in cancer Front Immunol, 11 (2020), p. 604

58 Y. Yang, C.W. Li, L.C. Chan, et al.Exosomal PD-L1 harbors active defense function to suppress T cell killing of breast cancer cells and promote tumor growth Cell Res, 28 (8) (2018), pp. 862-864

59 J. Monypenny, H. Milewicz, F. Flores-Borja, et al.ALIX regulates tumor-mediated immunosuppression by controlling EGFR activity and PD-L1 presentation Cell Rep, 24 (3) (2018), pp. 630-641

60 D.H. Kim, H. Kim, Y.J. Choi, et al.Exosomal PD-L1 promotes tumor growth through immune escape in non-small cell lung cancer Exp Mol Med, 51 (8) (2019), pp. 1-13

61 C. Sun, R. Mezzadra, T.N. SchumacherRegulation and function of the PD-L1 checkpoint Immunity, 48 (3) (2018), pp. 434-452

62 D. Daassi, K.M. Mahoney, G.J. FreemanThe importance of exosomal PDL1 in tumour immune evasion Nat Rev Immunol, 20 (4) (2020), pp. 209-215

63 X. Zhu, J. LangSoluble PD-1 and PD-L1:predictive and prognostic significance in cancer Oncotarget, 8 (57) (2017), pp. 97671-97682

64 J.W. Moon, S.K. Kong, B.S. Kim, et al.IFNγ induces PD-L1 overexpression by JAK2/STAT1/IRF-1 signaling in EBV-positive gastric carcinoma Sci Rep, 7 (2017), pp. 1-13

65 P. Dong, Y. Xiong, J. Yue, et al.Tumor-intrinsic PD-L1 signaling in cancer initiation, development and treatment: beyond immune evasion Front Oncol, 8 (2018), p. 386

66 G.L. SemenzaDefining the role of hypoxia-inducible factor 1 in cancer biology and therapeutics Oncogene, 29 (5) (2010), pp. 625-634

67 K. BalamuruganHIF-1 at the crossroads of hypoxia, inflammation, and cancer Int J Cancer, 138 (5) (2016), pp. 1058-1066

68 H.W. King, M.Z. Michael, J.M. GleadleHypoxic enhancement of exosome release by breast cancer cells BMC Cancer, 12 (2012), p. 421

69 M. Zhang, Y. Fan, X. Che, et al.5-FU-induced up regulation of exosomal PD-L1 causes immune suppression in advanced gastric cancer patients Front Oncol, 10 (2020), p. 492

70 M. Dosset, T.R. Vargas, A. Lagrange, et al.PD-1/PD-L1 pathway: an adaptive immune resistance mechanism to immunogenic chemotherapy in colorectal cancer OncoImmunology, 7 (6) (2018), Article e1433981

71 J. Liu, D. He, L. Cheng, et al.p300/CBP inhibition enhances the efficacy of programmed death-ligand 1 blockade treatment in prostate cancer Oncogene, 39 (19) (2020), pp. 3939-3951

72 E.J. Wherry, M. KurachiMolecular and cellular insights into T cell exhaustion Nat Rev Immunol, 15 (8) (2015), pp. 486-499

73 A. Ribas, J.D. WolchokCancer immunotherapy using checkpoint blockade Science, 359 (6382) (2018), pp. 1350-1355

74 A. Salmaninejad, S.F. Valilou, A.G. Shabgah, et al.PD-1/PD-L1 pathway: basic biology and role in cancer immunotherapy J Cell Physiol, 234 (10) (2019), pp. 16824-16837

75 M.N. Theodoraki, T.K. Hoffmann, T.L. WhitesideSeparation of plasma-derived exosomes into CD3(+) and CD3(-) fractions allows for association of immune cell and tumour cell markers with disease activity in HNSCC patients Clin Exp Immunol, 192 (3) (2018), pp. 271-283

76 F.L. Ricklefs, Q. Alayo, H. Krenzlin, et al.Immune evasion mediated by PD-L1 on glioblastoma-derived extracellular vesicles Sci Adv, 4 (3) (2018), p. eaar2766

77 J. Klibi, T. Niki, A. Riedel, et al.Blood diffusion and Th1-suppressive effects of galectin-9–containing exosomes released by Epstein-Barr virus–infected nasopharyngeal carcinoma cells Blood, 113 (9) (2009), pp. 1957-1966

78 D.D. Taylor, C. Gerçel-Taylor, K.S. Lyons, et al.T-cell apoptosis and suppression of T-cell receptor/CD3-zeta by Fas ligand-containing membrane vesicles shed from ovarian tumors Clin Cancer Res, 9 (14) (2003), pp. 5113-5119

79 M.N. Theodoraki, S.S. Yerneni, T.K. Hoffmann, et al.Clinical significance of PD-L1+ exosomes in plasma of head and neck cancer patients Clin Cancer Res, 24 (4) (2018), pp. 896-905

80 J. Wang, H. Zeng, H. Zhang, et al.The role of exosomal PD-L1 in tumor immunotherapy Transl Oncol, 14 (5) (2021), p. 101047

81 G. Wang, L. Xie, B. Li, et al.A nanounit strategy reverses immune suppression of exosomal PD-L1 and is associated with enhanced ferroptosis Nat Commun, 12 (2021), p. 5733

82 J.M. Shin, C.H. Lee, S. Son, et al.Sulfisoxazole elicits robust antitumour immune response along with immune checkpoint therapy by inhibiting exosomal PD-L1 Adv Sci, 9 (5) (2022), Article e2103245

83 C.H. Lee, J.H. Bae, E.J. Choe, et al.Macitentan improves antitumor immune responses by inhibiting the secretion of tumor-derived extracellular vesicle PD-L1 Theranostics, 12 (5) (2022), pp. 1971-1987

84 G.R. Monteith, D. McAndrew, H.M. Faddy, et al.Calcium and cancer: targeting Ca2+ transport Nat Rev Cancer, 7 (7) (2007), pp. 519-530

85 N.E. Saris, E. CarafoliA historical review of cellular calcium handling, with emphasis on mitochondria Biochem Mosc, 70 (2) (2005), pp. 187-194

86 T. CapiodCell proliferation, calcium influx and calcium channels Biochimie, 93 (12) (2011), pp. 2075-2079

87 S. Marchi, P. PintonAlterations of calcium homeostasis in cancer cells Curr Opin Pharmacol, 29 (2016), pp. 1-6

88 K. MikoshibaThe IP3 receptor/Ca2+ channel and its cellular function Biochem Soc Symp, 74 (2007), pp. 9-22

89 M. Prakriya, R.S. LewisStore-operated calcium channels Physiol Rev, 95 (4) (2015), pp. 1383-1436

90 C. Cui, J. Yang, L. Fu, et al.Progress in understanding mitochondrial calcium uniporter complex-mediated calcium signalling: a potential target for cancer treatment Br J Pharmacol, 176 (9) (2019), pp. 1190-1205

91 S. Orrenius, V. Gogvadze, B. ZhivotovskyCalcium and mitochondria in the regulation of cell death Biochem Biophys Res Commun, 460 (1) (2015), pp. 72-81

92 M. Zerial, H. McBrideRab proteins as membrane organizers Nat Rev Mol Cell Biol, 2 (2) (2001), pp. 107-117

93 Y. Tan, X. Luo, W. Lv, et al.Tumor-derived exosomal components: the multifaceted roles and mechanisms in breast cancer metastasis Cell Death Dis, 12 (6) (2021), p. 547

94 K.L. Boswell, D.J. James, J.M. Esquibel, et al.Munc13-4 reconstitutes calcium-dependent SNARE-mediated membrane fusion J Cell Biol, 197 (2) (2012), pp. 301-312

95 S.S. Woo, D.J. James, T.F.J. MartinMunc13-4 functions as a Ca2+ sensor for homotypic secretory granule fusion to generate endosomal exocytic vacuoles Mol Biol Cell, 28 (6) (2017), pp. 792-808

96 V.R. Minciacchi, M.R. Freeman, D. Di VizioExtracellular vesicles in cancer: exosomes, microvesicles and the emerging role of large oncosomes Semin Cell Dev Biol, 40 (2015), pp. 41-51

97 M. Catalano, L. O'DriscollInhibiting extracellular vesicles formation and release: a review of EV inhibitors J Extracell Vesicles, 9 (1) (2020), Article 1703244

98 N. Nishida-Aoki, N. Tominaga, F. Takeshita, et al.Disruption of circulating extracellular vesicles as a novel therapeutic strategy against cancer metastasis Mol Ther, 25 (1) (2017), pp. 181-191

99 A. Datta, H. Kim, M. Lal, et al.Manumycin A suppresses exosome biogenesis and secretion via targeted inhibition of Ras/Raf/ERK1/2 signaling and hnRNP H1 in castration-resistant prostate cancer cells Cancer Lett, 408 (2017), pp. 73-81

100 A. Bobrie, S. Krumeich, F. Reyal, et al.Rab27a supports exosome-dependent and-independent mechanisms that modify the tumor microenvironment and can promote tumor progression Cancer Res, 72 (19) (2012), pp. 4920-4930

101 A. Datta, H. Kim, L. McGee, et al.High-throughput screening identified selective inhibitors of exosome biogenesis and secretion: a drug repurposing strategy for advanced cancer Sci Rep, 8 (2018), p. 8161

102 E.J. Im, C.H. Lee, P.G. Moon, et al.Sulfisoxazole inhibits the secretion of small extracellular vesicles by targeting the endothelin receptor A Nat Commun, 10 (2019), p. 1387

103 J.L. Johnson, M. Ramadass, J. He, et al.Identification of neutrophil exocytosis inhibitors (nexinhibs), small molecule inhibitors of neutrophil exocytosis and inflammation J Biol Chem, 291 (50) (2016), pp. 25965-25982

104 T. Lallemand, M. Rouahi, A. Swiader, et al.nSMase2 (type 2-neutral sphingomyelinase) deficiency or inhibition by GW4869 reduces inflammation and atherosclerosis in Apoe-/- mice Arterioscler Thromb Vasc Biol, 38 (7) (2018), pp. 1479-1492

105 A. Takahashi, R. Okada, K. Nagao, et al.Exosomes maintain cellular homeostasis by excreting harmful DNA from cells Nat Commun, 8 (2017), p. 15287

106 F.M. Khan, E. Saleh, H. Alawadhi, et al.Inhibition of exosome release by ketotifen enhances sensitivity of cancer cells to doxorubicin Cancer Biol Ther, 19 (1) (2018), pp. 25-33

107 L. Ye, Z. Zhu, X. Chen, et al.The importance of exosomal PD-L1 in cancer progression and its potential as a therapeutic target Cells, 10 (11) (2021), p. 3247

108 A. Kulshreshtha, S. Singh, M. Ahmad, et al.Simvastatin mediates inhibition of exosome synthesis, localization and secretion via multicomponent interventions Sci Rep, 9 (2019), p. 16373

109 H.J. Kim, M.K. Park, S.Y. Kim, et al.Novel suppressive effects of ketotifen on migration and invasion of MDA-MB-231 and HT-1080 cancer cells Biomol Ther (Seoul), 22 (6) (2014), pp. 540-546

110 E.P. Spugnini, G. Citro, S. FaisProton pump inhibitors as anti vacuolar-ATPases drugs: a novel anticancer strategy J Exp Clin Cancer Res, 29 (1) (2010), p. 44

111 U.S. Kosgodage, R. Mould, A.B. Henley, et al.Cannabidiol (CBD) is a novel inhibitor for exosome and microvesicle (EMV) release in cancer Front Pharmacol, 9 (2018), p. 889

112 U.S. Kosgodage, P. Matewele, B. Awamaria, et al.Cannabidiol is a novel modulator of bacterial membrane vesicles Front Cell Infect Microbiol, 9 (2019), p. 324

113 R. Leblanc, R. Kashyap, K. Barral, et al.Pharmacological inhibition of syntenin PDZ2 domain impairs breast cancer cell activities and exosome loading with syndecan and EpCAM cargo J Extracell Vesicles, 10 (2) (2020), Article e12039

114 L. Wu, W. Lian, L. ZhaoCalcium signaling in cancer progression and therapy FEBS J, 288 (21) (2021), pp. 6187-6205

115 L. Racioppi, E.R. Nelson, W. Huang, et al.CaMKK2 in myeloid cells is a key regulator of the immune-suppressive microenvironment in breast cancer Nat Commun, 10 (2019), p. 2450

116 C. Weidinger, P.J. Shaw, S. FeskeSTIM1 and STIM2-mediated Ca2+ influx regulates antitumour immunity by CD8+ T cells EMBO Mol Med, 5 (9) (2013), pp. 1311-1321

117 K.D. Kim, S. Bae, T. Capece, et al.Targeted calcium influx boosts cytotoxic T lymphocyte function in the tumour microenvironment Nat Commun, 8 (2017), p. 15365

118 S.H. Jiang, L.L. Zhu, M. Zhang, et al.GABRP regulates chemokine signalling, macrophage recruitment and tumour progression in pancreatic cancer through tuning KCNN4-mediated Ca2+ signalling in a GABA-independent manner Gut, 68 (11) (2019), pp. 1994-2006

119 A. Maul-Pavicic, S.C.C. Chiang, A. Rensing-Ehl, et al.ORAI1-mediated calcium influx is required for human cytotoxic lymphocyte degranulation and target cell lysis Proc Natl Acad Sci U S A, 108 (8) (2011), pp. 3324-3329

120 A. Fiorio Pla, H.L. Ong, K.T. Cheng, et al.TRPV4 mediates tumor-derived endothelial cell migration via arachidonic acid-activated actin remodeling Oncogene, 31 (2) (2012), pp. 200-212

121 I. Azimi, M.J.G. Milevskiy, E. Kaemmerer, et al.TRPC1 is a differential regulator of hypoxia-mediated events and Akt signalling in PTEN-deficient breast cancer cells J Cell Sci, 130 (14) (2017), pp. 2292-2305

122 Y. Li, B. Guo, Q. Xie, et al.STIM1 mediates hypoxia-driven hepatocarcinogenesis via interaction with HIF-1 Cell Rep, 12 (3) (2015), pp. 388-395

123 S. Yu, Z. Xu, C. Zou, et al.Ion channel TRPM8 promotes hypoxic growth of prostate cancer cells via an O2-independent and RACK1-mediated mechanism of HIF-1α stabilization J Pathol, 234 (4) (2014), pp. 514-525

124 S. Li, J. Wang, Y. Wei, et al.Crucial role of TRPC6 in maintaining the stability of HIF-1α in glioma cells under hypoxia J Cell Sci, 128 (17) (2015), pp. 3317-3329

125 Y. Zhu, Q. Pan, H. Meng, et al.Enhancement of vascular endothelial growth factor release in long-term drug-treated breast cancer via transient receptor potential channel 5-Ca2+-hypoxia-inducible factor 1α pathway Pharmacol Res, 93 (2015), pp. 36-42

126 F. Sadras, G.R. Monteith, S.J. Roberts-ThomsonAn emerging role for calcium signaling in cancer-associated fibroblasts Int J Mol Sci, 22 (21) (2021), p. 11366

127 E. Vancauwenberghe, L. Noyer, S. Derouiche, et al.Activation of mutated TRPA1 ion channel by resveratrol in human prostate cancer associated fibroblasts (CAF) Mol Carcinog, 56 (8) (2017), pp. 1851-1867

128 M. Trebak, J.P. KinetCalcium signalling in T cells Nat Rev Immunol, 19 (3) (2019), pp. 154-169

129 P.C. Yang, M.S. JafriCa2+ signaling in T lymphocytes: the interplay of the endoplasmic reticulum, mitochondria, membrane potential, and CRAC channels on transcription factor activation Heliyon, 6 (3) (2020), Article e03526

130 P. Revy, M. Sospedra, B. Barbour, et al.Functional antigen-independent synapses formed between T cells and dendritic cells Nat Immunol, 2 (10) (2001), pp. 925-931

131 C.D. Surh, J. SprentRegulation of mature T cell homeostasis Semin Immunol, 17 (3) (2005), pp. 183-191

132 K. Omilusik, J. Priatel, X. Chen, et al.The CaV1.4 calcium channel is a critical regulator of T cell receptor signaling and naive T cell homeostasis Immunity, 35 (3) (2011), pp. 349-360

133 X. Shi, Y. Bi, W. Yang, et al.Ca2+ regulates T-cell receptor activation by modulating the charge property of lipids Nature, 493 (7430) (2013), pp. 111-115

134 X. He, C. XuImmune checkpoint signaling and cancer immunotherapy Cell Res, 30 (8) (2020), pp. 660-669

135 Q.J. Sheng, W.Y. Tian, X.G. Dou, et al.Programmed death 1, ligand 1 and 2 correlated genes and their association with mutation, immune infiltration and clinical outcomes of hepatocellular carcinoma World J Gastrointest Oncol, 12 (11) (2020), pp. 1255-1271

136 X. Chang, Y. DongCACNA1C is a prognostic predictor for patients with ovarian cancer J Ovarian Res, 14 (2021), p. 88

137 J.K. Byun, M. Park, S. Lee, et al.Inhibition of glutamine utilization synergizes with immune checkpoint inhibitor to promote antitumor immunity Mol Cell, 80 (4) (2020), pp. 592-606.e8

138 M. Tomé, A. Pappalardo, F. Soulet, et al.Inactivation of proprotein convertases in T cells inhibits PD-1 expression and creates a favorable immune microenvironment in colorectal cancer Cancer Res, 79 (19) (2019), pp. 5008-5021

139 L. Heim, J. Friedrich, M. Engelhardt, et al.NFATc1 promotes antitumoral effector functions and memory CD8+ T-cell differentiation during non-small cell lung cancer development Cancer Res, 78 (13) (2018), pp. 3619-3633

140 M.R. Sullivan, G.S. Ugolini, S. Sarkar, et al.Quantifying the efficacy of checkpoint inhibitors on CD8+ cytotoxic T cells for immunotherapeutic applications via single-cell interaction Cell Death Dis, 11 (11) (2020), p. 979

141 V. Volpin, T. Michels, A. Sorrentino, et al.CAMK1D triggers immune resistance of human tumor cells refractory to anti-PD-L1 treatment Cancer Immunol Res, 8 (9) (2020), pp. 1163-1179

142 Z. Chen, A. Krinsky, R.A. Woolaver, et al.TRAF3 acts as a checkpoint of B cell receptor signaling to control antibody class switch recombination and anergy J Immunol, 205 (3) (2020), pp. 830-841

143 X. Jiao, O. Nawab, T. Patel, et al.Recent advances targeting CCR5 for cancer and its role in immuno-oncology Cancer Res, 79 (19) (2019), pp. 4801-4807

144 J. Escandon Brehm, B. BedogniBlockade of CCR5 in melanoma: an alternative immune checkpoint modulator Exp Dermatol, 29 (2) (2020), p. 196

145 P. Sharma, J. AllisonImmune checkpoint targeting in cancer therapy: toward combination strategies with curative potential Cell, 161 (2) (2015), pp. 205-214

146 H. Borghaei, L. Paz-Ares, L. Horn, et al.Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer N Engl J Med, 373 (17) (2015), pp. 1627-1639

147 J.D. Wolchok, V. Chiarion-Sileni, R. Gonzalez, et al.Overall survival with combined nivolumab and ipilimumab in advanced melanoma N Engl J Med, 377 (14) (2017), pp. 1345-1356

148 R. Ferrari, R. Pavasini, P.G. Camici, et al.Anti-anginal drugs-beliefs and evidence: systematic review covering 50 years of medical treatment Eur Heart J, 40 (2) (2019), pp. 190-194

149 L. Wu, W. Lin, Q. Liao, et al.Calcium channel blocker nifedipine suppresses colorectal cancer progression and immune escape by preventing NFAT2 nuclear translocation Cell Rep, 33 (13) (2020), p. 108582

150 C. Li, H. Yao, H. Wang, et al.Repurposing screen identifies amlodipine as an inducer of PD-L1 degradation and antitumor immunity Oncogene, 40 (6) (2021), pp. 1128-1146

151 X. Pan, R. Li, H. Guo, et al.Dihydropyridine calcium channel blockers suppress the transcription of PD-L1 by inhibiting the activation of STAT1 Front Pharmacol, 11 (2021), p. 539261

152 M.R. Alam, J.I. Kim, C.H. Lee, et al.Characterization of immune checkpoint inhibition efficacy through inhibition of exosome secretion by calcium channel blockers in melanoma Yakhak Hoeji, 65 (4) (2021), pp. 313-320

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