Immunotherapy of Metastatic Mouse Breast Cancer by Adherent Splenocytes Pulsed With Extracts of Heated Tumor Cells and Lactobacillus Casei
Archives of Advances in Biosciences,
Vol. 13 No. 2 (2022),
1 January 2022
,
Page 1-9
https://doi.org/10.22037/aab.v13i.36298
Abstract
Introduction: Flask-adherent Splenocytes (SACs) fulfill antigen-presenting cell requirements
of acquired immune responses. This study was done to evaluate the efficacy of new
immunotherapy against breast cancer made by SACs pulsed with the extract of heated 4T1
cells and Lactobacillus casei, as a probiotic.
Materials and Methods: Mammary carcinoma was induced by injection of 4T1 cell line in
the flank of female Balb/c mice. The first SACs therapy was started on day 11 after tumor
induction when all animals had developed a palpable tumor. SACs therapy was done twice at
a 10-day interval.
Results: Mice with mammary tumors received SACs pulsed with combined heated 4T1 cells
and L. casei determined a more desirable survival curve and a slower rate of tumor development
compared to the other groups. At least 20% of the group receiving combined immunotherapy
were alive by day 58. Those mice receiving SACs pulsed with the Lysate of heated tumor
cells died by day 45.The maximum survival of other mice was up to 38 days after tumor
induction. Moreover, SAC pulsed with combined agents significantly amplified the secretion
of Interferon-γ (IFN-γ), and conversely reduced the secretion of Transforming growth factor-β
(TGF-β) and Interleukin 4 (IL-4) in the splenocyte population compared to splenocytes from
other groups. Combined immunotherapy increased the expression of p53 and caspase 3 genes
and reduced the exertion of BCL2 more than other immunotherapy protocols.
Conclusion: Immunotherapy with SACs pulsed with heated 4T1 cells and L. casei promotes
beneficial outcomes in the mouse model of breast cancer.
- Breast cancer, Immunotherapy, Apoptosis, Lactobacillus casei, Antigen- Presenting Cell, Spleen
How to Cite
References
Miricescu D, Totan A, Stanescu-Spinu II, Badoiu SC, Stefani C, Greabu M. PI3K/AKT/mTOR signaling pathway in breast cancer: From molecular landscape to clinical aspects. Int J Mol Sci. 2020; 22(1):173.[DOI:10.3390/ijms22010173] [PMID] [PMCID]
Koual M, Tomkiewicz C, Cano-Sancho G, Antignac JP, Bats AS, Coumoul X. Environmental chemicals, breast cancer progression and drug resistance. Environ Health. 2020; 19(1):117.[DOI:10.1186/s12940-020-00670-2] [PMID] [PMCID]
Hu C, Polley EC, Yadav S, Lilyquist J, Shimelis H, Na J, et al. The contribution of germline predisposition gene mutations to clinical subtypes of invasive breast cancer from a clinical genetic testing cohort. J Natl Cancer Inst. 2020; 112(12):1231-41. [DOI:10.1093/jnci/djaa023] [PMID] [PMCID]
Ulaner GA, Jhaveri K, Chandarlapaty S, Hatzoglou V, Riedl CC, Lewis JS, et al. Head-to-head evaluation of 18F-FES and 18F-FDG PET/CT in metastatic invasive lobular breast cancer. J Nucl Med. 2021; 62(3):326-31. [DOI:10.2967/jnumed.120.247882] [PMID] [PMCID]
Guo J, Duan Z, Zhang C, Wang W, He H, Liu Y, et al. Mouse 4T1 breast cancer cell-derived exosomes induce proinflammatory cytokine production in macrophages via miR-183. J Immunol. 2020; 205(10):2916-25. [DOI:10.4049/jimmunol.1901104] [PMID]
Jahangiri S, Abtahi Froushani SM, Delirezh N. Combination immunotherapy with extract of heated 4T1 and naloxone in mouse model of breast cancer. Turk J Med Sci. 2016; 46(2):518-23. [PMID]
Sadeghzadeh M, Bornehdeli S, Mohahammadrezakhani H, Abolghasemi M, Poursaei E, Asadi M, et al. Dendritic cell therapy in cancer treatment; the state-of-the-art. Life Sci. 2020; 254:117580. [DOI:10.1016/j.lfs.2020.117580] [PMID]
Harding CV, Canaday D, Ramachandra L. Choosing and preparing antigen-presenting cells. Curr Protoc Immunol. 2010; Chapter 16:Unit 16.1. [PMID]
Mirsanei Z, Habibi S, Kheshtchin N, Mirzaei R, Arab S, Zand B, et al. Optimized dose of dendritic cell-based vaccination in experimental model of tumor using artificial neural network. Iran J Allergy Asthma Immunol. 2020; 19(2):172-82. [DOI:10.18502/ijaai.v19i2.2770] [PMID]
Elean M, Albarracín L, Cataldo PG, Londero A, Kitazawa H, Saavedra L, et al. New immunobiotics from highly proteolytic Lactobacillus delbrueckii strains: Their impact on intestinal antiviral innate immune response. Benef Microbes. 2020; 11(4):375-90. [DOI:10.3920/BM2019.0198] [PMID]
Fukuyama K, Islam MA, Takagi M, Ikeda-Ohtsubo W, Kurata S, Aso H, et al. Evaluation of the immunomodulatory ability of lactic acid bacteria isolated from feedlot cattle against mastitis using a bovine mammary epithelial cells in vitro assay. Pathogens. 2020; 9(5):410. [DOI:10.3390/pathogens9050410] [PMID] [PMCID]
Riaz Rajoka MS, Zhao H, Mehwish HM, Li N, Lu Y, Lian Z, et al. Anti-tumor potential of cell free culture supernatant of Lactobacillus rhamnosus strains isolated from human breast milk. Food Res Int. 2019; 123:286-97. [DOI:10.1016/j.foodres.2019.05.002] [PMID]
Tonetti FR, Islam MA, Vizoso-Pinto MG, Takahashi H, Kitazawa H, Villena J. Nasal priming with immunobiotic lactobacilli improves the adaptive immune response against influenza virus. Int Immunopharmacol. 2020; 78:106115.[DOI:10.1016/j.intimp.2019.106115] [PMID]
Velikova T, Tumangelova-Yuzeir K, Georgieva R, Ivanova-Todorova E, Karaivanova E, Nakov V, et al. Lactobacilli supplemented with larch arabinogalactan and colostrum stimulates an immune response towards peripheral NK Activation and Gut tolerance. Nutrients. 2020; 12(6):1706. [DOI:10.3390/nu12061706] [PMID] [PMCID]
Sampsell K, Hao D, Reimer RA. The Gut microbiota: A potential gateway to improved health outcomes in breast cancer treatment and survivorship. Int J Mol Sci. 2020; 21(23):9239. [DOI:10.3390/ijms21239239] [PMID] [PMCID]
Lim JF, Berger H, Su I. Isolation and activation of murine lymphocytes. J Vis Exp. 2016; 116:e54596. [DOI:10.3791/54596]
Stagg AJ, Burke F, Hill S, Knight SC. Isolation of mouse spleen dendritic cells. Methods Mol Med. 2001; 64:9-22.[DOI:10.1385/1-59259-150-7:9] [PMID]
Knocke S, Fleischmann-Mundt B, Saborowski M, Manns MP, Kühnel F, Wirth TC, et al. Tailored tumor immunogenicity reveals regulation of CD4 and CD8 T cell responses against cancer. Cell Rep. 2016; 17(9):2234-46. [PMID]
Ebensen T, Delandre S, Prochnow B, Guzmán CA, Schulze K. The combination vaccine adjuvant system Alum/c-di-AMP results in quantitative and qualitative enhanced immune responses post immunization. Front Cell Infect Microbiol. 2019; 9:31. [DOI:10.3389/fcimb.2019.00031]
Saadeldin MK, Abdel-Aziz AK, Abdellatif A. Dendritic cell vaccine immunotherapy; the beginning of the end of cancer and COVID-19. A hypothesis. Med Hypotheses. 2021; 146:110365. [DOI:10.1016/j.mehy.2020.110365] [PMID] [PMCID]
De Maio A, Hightower LE. Heat shock proteins and the biogenesis of cellular membranes. Cell Stress Chaperones. 2021; 26(1):15-8. [DOI:10.1007/s12192-020-01173-2] [PMID] [PMCID]
Ahmed A, Tait SWG. Targeting immunogenic cell death in cancer. Mol Oncol. 2020; 14(12):2994-3006. [DOI:10.1002/1878-0261.12851] [PMID] [PMCID]
Junprung W, Supungul P, Tassanakajon A. Structure, gene expression, and putative functions of crustacean heat shock proteins in innate immunity. Dev Comp Immunol. 2021; 115:103875. [DOI:10.1016/j.dci.2020.103875] [PMID]
Drakes M, Blanchard T, Czinn S. Bacterial probiotic modulation of dendritic cells. Infect Immun. 2004; 72(6):3299-309.[DOI:10.1128/IAI.72.6.3299-3309.2004] [PMID] [PMCID]
Jafari S, Froushani SMA, Tokmachi A. Combined extract of heated 4T1 and a heat-killed preparation of lactobacillus casei in a mouse model of breast cancer. Iran J Med Sci. 2017; 42(5):457-64. [PMID]
Ratajczak C, Duez C, Grangette C, Pochard P, Tonnel AB, Pestel J. Impact of lactic Acid bacteria on dendritic cells from allergic patients in an experimental model of intestinal epithelium. J Biomed Biotechnol. 2007; 2007(1):71921. [DOI:10.1155/2007/71921] [PMID] [PMCID]
Mia S, Warnecke A, Zhang XM, Malmström V, Harris RA. An optimized protocol for human M2 macrophages using M-CSF and IL-4/IL-10/TGF-β yields a dominant immunosuppressive phenotype. Scand J Immunol. 2014; 79(5):305-14. [DOI:10.1111/sji.12162] [PMID] [PMCID]
Delgado-Ramirez Y, Colly V, Gonzalez GV, Leon-Cabrera S. Signal transducer and activator of transcription 6 as a target in colon cancer therapy. Oncol Lett. 2020; 20(1):455-64. [DOI:10.3892/ol.2020.11614] [PMID] [PMCID]
Zeng G, Jin L, Ying Q, Chen H, Thembinkosi MC, Yang C, et al. Regulatory T cells in cancer immunotherapy: Basic research outcomes and clinical directions. Cancer Manag Res. 2020; 12:10411-21. [DOI:10.2147/CMAR.S265828] [PMID] [PMCID]
Changizi Z, Moslehi A, Rohani AH, Eidi A. Chlorogenic acid induces 4T1 breast cancer tumor’s apoptosis via p53, Bax, Bcl-2, and caspase-3 signaling pathways in BALB/c mice. J Biochem Mol Toxicol. 2021; 35(2):e22642. [DOI:10.1002/jbt.22642] [PMID]
Ke H, Wang X, Zhou Z, Ai W, Wu Z, Zhang Y. Effect of weimaining on apoptosis and Caspase-3 expression in a breast cancer mouse model. J Ethnopharmacol. 2021; 264:113363.[DOI:10.1016/j.jep.2020.113363] [PMID]
Jiang M, Qi L, Li L, Li Y. The caspase-3/GSDME signal pathway as a switch between apoptosis and pyroptosis in cancer. Cell Death Discov. 2020; 6:112. [DOI:10.1038/s41420-020-00349-0] [PMID] [PMCID]
Roberts AW. Therapeutic development and current uses of BCL-2 inhibition. Hematology Am Soc Hematol Educ Program. 2020; 2020(1):1-9. [DOI:10.1182/hematology.2020000154] [PMID] [PMCID]
Zhu G, Pan C, Bei JX, Li B, Liang C, Xu Y, et al. Mutant p53 in cancer progression and targeted therapies. Front Oncol. 2020; 10:595187. [DOI:10.3389/fonc.2020.595187] [PMID] [PMCID]
Cao Y, Wang X, Jin T, Tian Y, Dai C, Widarma C, et al. Immune checkpoint molecules in natural killer cells as potential targets for cancer immunotherapy. Signal Transduct Target Ther. 2020; 5(1):250. [DOI:10.1038/s41392-020-00348-8] [PMID] [PMCID]
- Abstract Viewed: 223 times
- PDF Downloaded: 29 times
- MP3 Downloaded: 12 times