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Critical Adjuvant Influences on Preventive Anti-Metastasis Vaccine Using a Structural Epitope Derived from Membrane Type Protease PRSS14

  • Ki Yeon Kim (Department of Biological Sciences, Inha University) ;
  • Eun Hye Cho (Department of Biological Sciences, Inha University) ;
  • Minsang Yoon (Department of Biological Sciences, Inha University) ;
  • Moon Gyo Kim (Department of Biological Sciences, Inha University)
  • Received : 2020.04.26
  • Accepted : 2020.07.28
  • Published : 2020.08.31
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Abstract

We tested how adjuvants effect in a cancer vaccine model using an epitope derived from an autoactivation loop of membrane-type protease serine protease 14 (PRSS14; loop metavaccine) in mouse mammary tumor virus (MMTV)-polyoma middle tumor-antigen (PyMT) system and in 2 other orthotopic mouse systems. Earlier, we reported that loop metavaccine effectively prevented progression and metastasis regardless of adjuvant types and TH types of hosts in tail-vein injection systems. However, the loop metavaccine with Freund's complete adjuvant (CFA) reduced cancer progression and metastasis while that with alum, to our surprise, were adversely affected in 3 tumor bearing mouse models. The amounts of loop peptide specific antibodies inversely correlated with tumor burden and metastasis, meanwhile both TH1 and TH2 isotypes were present regardless of host type and adjuvant. Tumor infiltrating myeloid cells such as eosinophil, monocyte, and neutrophil were asymmetrically distributed among 2 adjuvant groups with loop metavaccine. Systemic expression profiling using the lymph nodes of the differentially immunized MMTV-PyMT mouse revealed that adjuvant types, as well as loop metavaccine can change the immune signatures. Specifically, loop metavaccine itself induces TH2 and TH17 responses but reduces TH1 and Treg responses regardless of adjuvant type, whereas CFA but not alum increased follicular TH response. Among the myeloid signatures, eosinophil was most distinct between CFA and alum. Survival analysis of breast cancer patients showed that eosinophil chemokines can be useful prognostic factors in PRSS14 positive patients. Based on these observations, we concluded that multiple immune parameters are to be considered when applying a vaccine strategy to cancer patients.

Keywords

Acknowledgement

We thank all of the LMCI members who helped in data generation and in analyses. This work was supported by a Korean Government Grant (NRF-2017R1A2B4008109) and an Inha University Research Grant.

References

  1. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell 2011;144:646-674. https://doi.org/10.1016/j.cell.2011.02.013
  2. Schreiber RD, Old LJ, Smyth MJ. Cancer immunoediting: integrating immunity's roles in cancer suppression and promotion. Science 2011;331:1565-1570. https://doi.org/10.1126/science.1203486
  3. Lewis CE, Pollard JW. Distinct role of macrophages in different tumor microenvironments. Cancer Res 2006;66:605-612. https://doi.org/10.1158/0008-5472.CAN-05-4005
  4. Sionov RV, Fridlender ZG, Granot Z. The multifaceted roles neutrophils play in the tumor microenvironment. Cancer Microenviron 2015;8:125-158. https://doi.org/10.1007/s12307-014-0147-5
  5. Kim HJ, Cantor H. CD4 T-cell subsets and tumor immunity: the helpful and the not-so-helpful. Cancer Immunol Res 2014;2:91-98.
  6. Chraa D, Naim A, Olive D, Badou A. T lymphocyte subsets in cancer immunity: friends or foes. J Leukoc Biol 2019;105:243-255. https://doi.org/10.1002/JLB.MR0318-097R
  7. Ise W, Fujii K, Shiroguchi K, Ito A, Kometani K, Takeda K, Kawakami E, Yamashita K, Suzuki K, Okada T, et al. T follicular helper cell-germinal center B cell interaction strength regulates entry into plasma cell or recycling germinal center cell fate. Immunity 2018;48:702-715.e4. https://doi.org/10.1016/j.immuni.2018.03.027
  8. Billiau A, Matthys P. Modes of action of Freund's adjuvants in experimental models of autoimmune diseases. J Leukoc Biol 2001;70:849-860. https://doi.org/10.1189/jlb.70.6.849
  9. Kim KY, Yoon M, Cho Y, Lee KH, Park S, Lee SR, Choi SY, Lee D, Yang C, Cho EH, et al. Targeting metastatic breast cancer with peptide epitopes derived from autocatalytic loop of Prss14/ST14 membrane serine protease and with monoclonal antibodies. J Exp Clin Cancer Res 2019;38:363.
  10. Di Pasquale A, Preiss S, Tavares Da Silva F, Garcon N. Vaccine adjuvants: from 1920 to 2015 and beyond. Vaccines (Basel) 2015;3:320-343. https://doi.org/10.3390/vaccines3020320
  11. Marrack P, McKee AS, Munks MW. Towards an understanding of the adjuvant action of aluminium. Nat Rev Immunol 2009;9:287-293.
  12. Tomljenovic L, Shaw CA. Aluminum vaccine adjuvants: are they safe? Curr Med Chem 2011;18:2630-2637. https://doi.org/10.2174/092986711795933740
  13. Darbre PD, Mannello F, Exley C. Aluminium and breast cancer: sources of exposure, tissue measurements and mechanisms of toxicological actions on breast biology. J Inorg Biochem 2013;128:257-261. https://doi.org/10.1016/j.jinorgbio.2013.07.005
  14. Kim MG, Chen C, Lyu MS, Cho EG, Park D, Kozak C, Schwartz RH. Cloning and chromosomal mapping of a gene isolated from thymic stromal cells encoding a new mouse type II membrane serine protease, epithin, containing four LDL receptor modules and two CUB domains. Immunogenetics 1999;49:420-428. https://doi.org/10.1007/s002510050515
  15. Lin CY, Anders J, Johnson M, Sang QA, Dickson RB. Molecular cloning of cDNA for matriptase, a matrix-degrading serine protease with trypsin-like activity. J Biol Chem 1999;274:18231-18236. https://doi.org/10.1074/jbc.274.26.18231
  16. Takeuchi T, Shuman MA, Craik CS. Reverse biochemistry: use of macromolecular protease inhibitors to dissect complex biological processes and identify a membrane-type serine protease in epithelial cancer and normal tissue. Proc Natl Acad Sci U S A 1999;96:11054-11061. https://doi.org/10.1073/pnas.96.20.11054
  17. Benaud CM, Oberst M, Dickson RB, Lin CY. Deregulated activation of matriptase in breast cancer cells. Clin Exp Metastasis 2002;19:639-649. https://doi.org/10.1023/A:1020985632550
  18. Bergum C, Zoratti G, Boerner J, List K. Strong expression association between matriptase and its substrate prostasin in breast cancer. J Cell Physiol 2012;227:1604-1609. https://doi.org/10.1002/jcp.22877
  19. Kauppinen JM, Kosma VM, Soini Y, Sironen R, Nissinen M, Nykopp TK, Karja V, Eskelinen M, Kataja V, Mannermaa A. ST14 gene variant and decreased matriptase protein expression predict poor breast cancer survival. Cancer Epidemiol Biomarkers Prev 2010;19:2133-2142. https://doi.org/10.1158/1055-9965.EPI-10-0418
  20. Welman A, Sproul D, Mullen P, Muir M, Kinnaird AR, Harrison DJ, Faratian D, Brunton VG, Frame MC. Diversity of matriptase expression level and function in breast cancer. PLoS One 2012;7:e34182.
  21. Kim S, Yang JW, Kim C, Kim MG. Impact of suppression of tumorigenicity 14 (ST14)/serine protease 14 (Prss14) expression analysis on the prognosis and management of estrogen receptor negative breast cancer. Oncotarget 2016;7:34643-34663. https://doi.org/10.18632/oncotarget.9155
  22. Zoratti GL, Tanabe LM, Varela FA, Murray AS, Bergum C, Colombo E, Lang JE, Molinolo AA, Leduc R, Marsault E, et al. Targeting matriptase in breast cancer abrogates tumour progression via impairment of stromal-epithelial growth factor signalling. Nat Commun 2015;6:6776.
  23. Kim C, Lee HS, Lee D, Lee SD, Cho EG, Yang SJ, Kim SB, Park D, Kim MG. Epithin/PRSS14 proteolytically regulates angiopoietin receptor Tie2 during transendothelial migration. Blood 2011;117:1415-1424. https://doi.org/10.1182/blood-2010-03-275289
  24. Bugge TH, Antalis TM, Wu Q. Type II transmembrane serine proteases. J Biol Chem 2009;284:23177-23181. https://doi.org/10.1074/jbc.R109.021006
  25. Martin CE, List K. Cell surface-anchored serine proteases in cancer progression and metastasis. Cancer Metastasis Rev 2019;38:357-387.
  26. Franzen O, Gan LM, Bjorkegren JL. PanglaoDB: a web server for exploration of mouse and human single-cell RNA sequencing data. Database (Oxford) 2019;2019:610-619.
  27. Geissmann F, Jung S, Littman DR. Blood monocytes consist of two principal subsets with distinct migratory properties. Immunity 2003;19:71-82. https://doi.org/10.1016/S1074-7613(03)00174-2
  28. Palframan RT, Jung S, Cheng G, Weninger W, Luo Y, Dorf M, Littman DR, Rollins BJ, Zweerink H, Rot A, et al. Inflammatory chemokine transport and presentation in HEV: a remote control mechanism for monocyte recruitment to lymph nodes in inflamed tissues. J Exp Med 2001;194:1361-1373. https://doi.org/10.1084/jem.194.9.1361
  29. Sunderkotter C, Nikolic T, Dillon MJ, Van Rooijen N, Stehling M, Drevets DA, Leenen PJ. Subpopulations of mouse blood monocytes differ in maturation stage and inflammatory response. J Immunol 2004;172:4410-4417.
  30. Wu RQ, Zhang DF, Tu E, Chen QM, Chen W. The mucosal immune system in the oral cavity-an orchestra of T cell diversity. Int J Oral Sci 2014;6:125-132. https://doi.org/10.1038/ijos.2014.48
  31. Jablonski KA, Amici SA, Webb LM, Ruiz-Rosado JD, Popovich PG, Partida-Sanchez S, Guerau-de-Arellano M. Novel markers to delineate murine M1 and M2 macrophages. PLoS One 2015;10:e0145342.
  32. Rose S, Misharin A, Perlman H. A novel Ly6C/Ly6G-based strategy to analyze the mouse splenic myeloid compartment. Cytometry A 2012;81A:343-350. https://doi.org/10.1002/cyto.a.22012
  33. Saja MF, Baudino L, Jackson WD, Cook HT, Malik TH, Fossati-Jimack L, Ruseva M, Pickering MC, Woollard KJ, Botto M. Triglyceride-rich lipoproteins modulate the distribution and extravasation of Ly6C/Gr1low monocytes. Cell Reports 2015;12:1802-1815. https://doi.org/10.1016/j.celrep.2015.08.020
  34. Nussbaum JC, Van Dyken SJ, von Moltke J, Cheng LE, Mohapatra A, Molofsky AB, Thornton EE, Krummel MF, Chawla A, Liang HE, et al. Type 2 innate lymphoid cells control eosinophil homeostasis. Nature 2013;502:245-248.