Candida Albicans Activated Splenocytes Promote Strong Immune Responses in a Murine Model of Breast Cancer
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Abstract
Introduction: The potential of Candida albicans to modulate antigen-presenting cells maturation has been documented in past studies. Dendritic cells are critical modulators in the orchestration of adaptive immune responses alongside myeloid subtypes, which play an important role in the presentation of antigens to T cells. The aim of this study was to evaluate the efficacy of splenocytes activated with the extract of heated 4T1 cells and the yeast form of C. albicans against breast cancer growth in vivo.Methods: 4T1 cells were subcutaneously injected into the left flanks of female BALB/c mice (n=40). At a time when palpable tumors had developed, experimental groups were immunized twice at one-week interim with either activated splenocytes with the extract of heated 4T1 or the killed preparation of yeast form of C. albicans or a combination of the two-One week after the second injection, one-half of animals (n=20) were euthanized to investigate the immune response profile. Results: Administration of activated splenocytes with the combination protocol caused a favorable survival curve and slower rates of tumor development compared to other tumor-bearing mice. Moreover, combination therapy significantly increased the secretion of IFN-γ, respiratory burst and nitric oxide production and conversely diminished the secretion of IL-4, IL-10 and TGF-β in the splenocyte population.Conclusions: Since the murine 4T1 cell line is similar to the final stage of human breast carcinoma, we postulate that activated splenocytes with the extract of heated 4T1 cells and yeast form of C. albicans can reduce tumor development in tumor-bearing mice.
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24. Coluccio AE, Rodriguez RK, Kernan MJ, Neiman AM. The Yeast Spore Wall Enables Spores to Survive Passage through the Digestive Tract of Drosophila. PLoS ONE. 2008;3(8):e2873.
25. Glomski IJ, Fritz JH, Keppler SJ, Balloy V, Chignard M, Mock M, et al. Murine splenocytes produce inflammatory cytokines in a MyD88-dependent response to Bacillus anthracis spores. Cellular microbiology. 2007;9(2):502-13.
26. Chaffin WL, López-Ribot JL, Casanova M, Gozalbo D, Martínez JP. Cell wall and secreted proteins of Candida albicans: identification, function, and expression. Microbiology and molecular biology reviews : MMBR. 1998;62(1):130-80.
27. Carvalho MI, Pires I, Prada J. A role for T-lymphocytes in human breast cancer and in canine mammary tumors. 2014;2014:130894.
28. Criscitiello C, Curigliano G. Immunotherapy of Breast Cancer. Progress in tumor research. 2015;42:30-43.
29. Barbera Betancourt A, Lyu Q, Broere F, Sijts A, Rutten V, van Eden W. T Cell-Mediated Chronic Inflammatory Diseases Are Candidates for Therapeutic Tolerance Induction with Heat Shock Proteins. Frontiers in immunology. 2017;8:1408.
30. Khabbazi S, Goumon Y, Parat MO. Morphine Modulates Interleukin-4- or Breast Cancer Cell-induced Pro-metastatic Activation of Macrophages. Scientific reports. 2015;5:11389.
2. Tao K, Fang M, Alroy J, Sahagian GG. Imagable 4T1 model for the study of late stage breast cancer. BMC cancer. 2008;8:228.
3. Hey Y-Y, Quah B, O’Neill HC. Antigen presenting capacity of murine splenic myeloid cells. BMC Immunology. 2017;18:4.
4. Hey YY, Tan JK, O'Neill HC. Redefining Myeloid Cell Subsets in Murine Spleen. Frontiers in immunology. 2015;6:652.
5. Shang N, Figini M, Shangguan J, Wang B, Sun C, Pan L, et al. Dendritic cells based immunotherapy. American journal of cancer research. 2017;7(10):2091-102.
6. Constantino J, Gomes C, Falcao A, Neves BM, Cruz MT. Dendritic cell-based immunotherapy: a basic review and recent advances. Immunologic research. 2017;65(4):798-810.
7. Maueroder C, Munoz LE, Chaurio RA, Herrmann M, Schett G, Berens C. Tumor Immunotherapy: Lessons from Autoimmunity. Frontiers in immunology. 2014;5:212.
8. Thompson DS, Carlisle PL, Kadosh D. Coevolution of Morphology and Virulence in Candida Species. Eukaryotic Cell. 2011;10(9):1173-82.
9. Newman SL, Holly A. Candida albicans Is Phagocytosed, Killed, and Processed for Antigen Presentation by Human Dendritic Cells. Infection and immunity. 2001;69(11):6813-22.
10. Torosantucci A, Romagnoli G, Chiani P, Stringaro A, Crateri P, Mariotti S, et al. Candida albicans yeast and germ tube forms interfere differently with human monocyte differentiation into dendritic cells: a novel dimorphism-dependent mechanism to escape the host's immune response. Infection and immunity. 2004;72(2):833-43.
11. Wood LM, PATERSON Y. Attenuated Listeria monocytogenes: A Powerful and Versatile Vector for the Future of Tumor Immunotherapy. Frontiers in Cellular and Infection Microbiology. 2014;4.
12. Xu HM. Th1 cytokine-based immunotherapy for cancer. Hepatobiliary & pancreatic diseases international : HBPD INT. 2014;13(5):482-94.
13. Lu L, Hsieh M, Oriss TB, Morel PA, Starzl TE, Rao AS, et al. Generation of DC from mouse spleen cell cultures in response to GM-CSF: immunophenotypic and functional analyses. Immunology. 1995;84(1):127-34.
14. Jahangiri S, Abtahi Froushani SM, Delirezh N. Combination immunotherapy with extract of heated 4T1 and naloxone in mouse model of breast cancer. Turkish journal of medical sciences. 2016;46(2):518-23.
15. Abtahi Froushani SM, Delirezh N, Hobbenaghi R, Mosayebi G. Synergistic effects of atorvastatin and all-trans retinoic acid in ameliorating animal model of multiple sclerosis. Immunological investigations. 2014;43(1):54-68.
16. Shushtari N, Abtahi Froushani SM. Caffeine Augments The Instruction of Anti-Inflammatory Macrophages by The Conditioned Medium of Mesenchymal Stem Cells. Cell journal. 2017;19(3):415-24.
17. Dowling JK, Mansell A. Toll-like receptors: the swiss army knife of immunity and vaccine development. Clinical & translational immunology. 2016;5(5):e85.
18. Vasou A, Sultanoglu N, Goodbourn S, Randall RE, Kostrikis LG. Targeting Pattern Recognition Receptors (PRR) for Vaccine Adjuvantation: From Synthetic PRR Agonists to the Potential of Defective Interfering Particles of Viruses. Viruses. 2017;9(7).
19. Khamisabadi M, Arab S, Motamedi M, Khansari N, Moazzeni SM, Gheflati Z, et al. Listeria monocytogenes activated dendritic cell based vaccine for prevention of experimental tumor in mice. Iranian journal of immunology : IJI. 2008;5(1):36-44.
20. Milani V, Noessner E, Ghose S, Kuppner M, Ahrens B, Scharner A, et al. Heat shock protein 70: role in antigen presentation and immune stimulation. International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group. 2002;18(6):563-75.
21. Kelly M, McNeel D, Fisch P, Malkovsky M. Immunological considerations underlying heat shock protein-mediated cancer vaccine strategies. Immunology letters. 2017;193:1-10.
22. Bausero MA, Page DT, Osinaga E, Asea A. Surface expression of Hsp25 and Hsp72 differentially regulates tumor growth and metastasis. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine. 2004;25(5-6):243-51.
23. Bromuro C, La Valle R, Sandini S, Urbani F, Ausiello CM, Morelli L, et al. A 70-Kilodalton Recombinant Heat Shock Protein of Candida albicans Is Highly Immunogenic and Enhances Systemic Murine Candidiasis. Infection and immunity. 1998;66(5):2154-62.
24. Coluccio AE, Rodriguez RK, Kernan MJ, Neiman AM. The Yeast Spore Wall Enables Spores to Survive Passage through the Digestive Tract of Drosophila. PLoS ONE. 2008;3(8):e2873.
25. Glomski IJ, Fritz JH, Keppler SJ, Balloy V, Chignard M, Mock M, et al. Murine splenocytes produce inflammatory cytokines in a MyD88-dependent response to Bacillus anthracis spores. Cellular microbiology. 2007;9(2):502-13.
26. Chaffin WL, López-Ribot JL, Casanova M, Gozalbo D, Martínez JP. Cell wall and secreted proteins of Candida albicans: identification, function, and expression. Microbiology and molecular biology reviews : MMBR. 1998;62(1):130-80.
27. Carvalho MI, Pires I, Prada J. A role for T-lymphocytes in human breast cancer and in canine mammary tumors. 2014;2014:130894.
28. Criscitiello C, Curigliano G. Immunotherapy of Breast Cancer. Progress in tumor research. 2015;42:30-43.
29. Barbera Betancourt A, Lyu Q, Broere F, Sijts A, Rutten V, van Eden W. T Cell-Mediated Chronic Inflammatory Diseases Are Candidates for Therapeutic Tolerance Induction with Heat Shock Proteins. Frontiers in immunology. 2017;8:1408.
30. Khabbazi S, Goumon Y, Parat MO. Morphine Modulates Interleukin-4- or Breast Cancer Cell-induced Pro-metastatic Activation of Macrophages. Scientific reports. 2015;5:11389.
| Files | ||
| Issue | Vol 11 No 3 (2019) | |
| Section | Original Articles | |
| DOI | https://doi.org/10.18502/bccr.v11i3.5719 | |
| Keywords | ||
| 4T1 Breast cancer Candida albicans Dendritic cell Macrophage | ||
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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
Mashhouri S, Yarahmadi E, Abtahi Froushani SM. Candida Albicans Activated Splenocytes Promote Strong Immune Responses in a Murine Model of Breast Cancer. Basic Clin Cancer Res. 2019;11(3):113-123.
