Abstract
Cancer immune-therapy is an interesting avenue of studying the effects of deviating immune system responses to achieve the desired result. Lactobacilli are inhabitants of the GI tract which have shown beneficial health effects on various ailments including malignancies. Their mechanisms of action comprise a very intense area of research. In this study we evaluated the immunomodulatory effects of Lactobacillus acidophilus in in vivo model of breast cancer. Lactobacillus acidophilus (L.a) was isolated from traditional home-made yogurt and also from neonatal stool by aerobic overnight culture at 37°C in MRS broth. Delayed Type Hypersensitivity (DTH) assay was performed to find the best immunostimulant dose. 4T1 tumour bearing mice were treated with 2 × 108 cfu of isolated L. acidophilus and 20 mg/kg Cyclophosphamide for 15 consecutive days. Tumour volume was measured using a digital vernier calliper. Lymphocyte proliferation was done using MTT proliferation assay. Production of IFNγ, IL-4 and TGF-β from cultured Splenocytes was assessed in the presence of purified tumour antigen. According to results administration of L.a induced a significant decrease in tumour growth pattern (P value = 0.00). Significant alterations in splenocyte production of IFN-γ, IL-4 and TGf-β (P values < 0.05) and also lymphocyte proliferation in L.a treated animals was evident (P value < 0.05). This study indicated that oral administration of L.a is able to alter the cytokine production in tumour bearing mice into a Th1 protective pattern, favourable to anti tumour immunity. Reduced tumour growth rate and increased lymphocyte proliferation are also thus supportive. Further studies are required to elucidate the exact mechanism by which local actions of probiotics affect the systemic immune responses against transformed cells.
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References
Gilboa E. DC-based cancer vaccines. J Clin Investig. 2007;117(5):1195.
Smits ELJM, Anguille S, Cools N, Berneman ZN, Van Tendeloo VFI. Dendritic cell-based cancer gene therapy. Hum Gene Ther. 2009;20(10):1106–18.
Huang FP, Chen YX, To CKW. Guiding the “misguided”–functional conditioning of dendritic cells for the DC–based immunotherapy against tumours. Eur J Immunol. 2011.
Smith FO, Klapper JA, Wunderlich JR, Rosenberg SA, Dudley ME. Impact of a recombinant fowlpox vaccine on the efficacy of adoptive cell therapy with tumor infiltrating lymphocytes in a patient with metastatic melanoma. J Immunother. 2009;32(8):870.
Mondino A, Dardalhon V, Michelini RH, Loisel-Meyer S, Taylor N. Redirecting the immune response: role of adoptive T cell therapy. Hum Gene Ther. 2010;21(5):533–41.
Klebanoff CA, Gattinoni L, Palmer DC, Muranski P, Ji Y, Hinrichs CS, et al. Determinants of successful CD8+ T-cell adoptive immunotherapy for large established tumors in mice. Clin Cancer Res. 2011;17(16):5343.
Kirkwood JM, Lee S, Moschos SJ, Albertini MR, Michalak JC, Sander C, et al. Immunogenicity and antitumor effects of vaccination with peptide vaccine+/− granulocyte-monocyte colony-stimulating factor and/or IFN-α2b in advanced metastatic melanoma: eastern cooperative oncology group phase II trial E1696. Clin Cancer Res. 2009;15(4):1443–51.
Zarei S, Schwenter F, Luy P, Aurrand-Lions M, Morel P, Kopf M, et al. Role of GM-CSF signaling in cell-based tumor immunization. Blood. 2009;113(26):6658–68.
Collado MC, Isolauri E, Salminen S, Sanz Y. The impact of probiotic on gut health. Curr Drug Metabol. 2009;10(1):68–78.
Schiavi E, Barletta B, Barone A, Butteroni C, Corinti S, Di Felice G. Probiotic treatment induces intestinal regulatory dendritic and T cells, and counter-regulates Th2 responses and anaphylaxis in a mouse model of food allergy. Clin Transl Allergy. 2011;1:1.
Kalliomäki M, Isolauri E. Role of intestinal flora in the development of allergy. Curr Opin Allergy Clin Immunol. 2003;3(1):15.
Fedorak RN, Dieleman LA, Madsen KL. Prebiotics, probiotics, antibiotics, and nutritional therapies in IBD. Inflamm Bowel Dis. 2011:123–50.
Stephani J, Radulovic K, Niess JH. Gut Microbiota, Probiotics and Inflammatory Bowel Disease. Archivum immunologiae et therapiae experimentalis. 2011:1–17.
Liong MT. Roles of probiotics and prebiotics in colon cancer prevention: postulated mechanisms and in-vivo evidence. Int J Mol Sci. 2008;9(5):854–63.
Oelschlaeger TA. Mechanisms of probiotic actions-a review. Int J Med Microbiol. 2010;300(1):57–62.
Gill H, Prasad J. Probiotics, immunomodulation, and health benefits. Bioact Compon Milk. 2008:423–54.
Chiba Y, Shida K, Nagata S, Wada M, Bian L, Wang C, et al. Well–controlled proinflammatory cytokine responses of Peyer’s patch cells to probiotic lactobacillus casei. Immunology. 2010;130(3):352–62.
Braat H, van den Brande J, van Tol E, Hommes D, Peppelenbosch M, van Deventer S. Lactobacillus rhamnosus induces peripheral hyporesponsiveness in stimulated CD4+ T cells via modulation of dendritic cell function. Am J Clin Nutr. 2004;80(6):1618.
Torii A, Torii S, Fujiwara S, Tanaka H, Inagaki N, Nagai H. Lactobacillus acidophilus strain L-92 regulates the production of Th1 cytokine as well as Th2 cytokines. Allergol Int. 2007;56(3):293–301.
Wallace TD, Bradley S, Buckley ND, Green-Johnson JM. Interactions of lactic acid bacteria with human intestinal epithelial cells: effects on cytokine production. J Food Protect. 2003;66(3):466–72.
Haller D, Bode C, Hammes W, Pfeifer A, Schiffrin E, Blum S. Non-pathogenic bacteria elicit a differential cytokine response by intestinal epithelial cell/leucocyte co-cultures. Gut. 2000;47(1):79.
Galdeano CM, Perdigon G. The probiotic bacterium lactobacillus casei induces activation of the gut mucosal immune system through innate immunity. Clin Vaccine Immunol. 2006;13(2):219–26.
Maassen C, van Holten-Neelen C, Balk F, Heijne den Bak-Glashouwer MJ, Leer RJ, Laman JD, et al. Strain-dependent induction of cytokine profiles in the gut by orally administered lactobacillus strains. Vaccine. 2000;18(23):2613–23.
Prescott S, Wickens K, Westcott L, Jung W, Currie H, Black P, et al. Supplementation with lactobacillus rhamnosus or bifidobacterium lactis probiotics in pregnancy increases cord blood interferon–γ and breast milk transforming growth factor–β and immunoglobin A detection. Clin Exp Allergy. 2008;38(10):1606–14.
Chuang L, Wu KG, Pai C, Hsieh PS, Tsai JJ, Yen JH, et al. Heat-killed cells of lactobacilli skew the immune response toward T helper 1 polarization in mouse splenocytes and dendritic cell-treated T cells. J Agric Food Chem. 2007;55(26):11080–6.
Easo J, Measham J, Munroe J, Green-Johnson J. Immunostimulatory actions of lactobacilli: mitogenic induction of antibody production and spleen cell proliferation by lactobacillus delbrueckii subsp. Bulgaricus and lactobacillus acidophilus. Food Agric Immunol. 2002;14(1):73–83.
Takagi A, Matsuzaki T, Sato M, Nomoto K, Morotomi M, Yokokura T. Enhancement of natural killer cytotoxicity delayed murine carcinogenesis by a probiotic microorganism. Carcinogenesis. 2001;22(4):599.
Cheon S, Lee KW, Kim KE, Park JK, Park S, Kim C, et al. Heat-killed Lactobacillus acidophilus La205 enhances NK cell cytotoxicity through increased granule exocytosis. Immunology Letters. 2011.
Yazdi MH, Dallal MMS, Hassan ZM, Holakuyee M, Amiri SA, Abolhassani M, et al. Oral administration of lactobacillus acidophilus induces IL-12 production in spleen cell culture of BALB/c mice bearing transplanted breast tumour. Br J Nutr. 2010;104(2):227–32.
Murosaki S, Muroyama K, Yamamoto Y, Yoshikai Y. Antitumor effect of heat-killed lactobacillus plantarum L-137 through restoration of impaired interleukin-12 production in tumor-bearing mice. Canc Immunol Immunother. 2000;49(3):157–64.
O’Hara RJ, Greenman J, MacDonald AW, Gaskell KM, Topping KP, Duthie GS, et al. Advanced colorectal cancer is associated with impaired interleukin 12 and enhanced interleukin 10 production. Clin Cancer Res. 1998;4(8):1943–8.
Gill HS, Rutherfurd KJ, Prasad J, Gopal PK. Enhancement of natural and acquired immunity by lactobacillus rhamnosus (HN001), lactobacillus acidophilus (HN017) and bifidobacterium lactis (HN019). Br J Nutr. 2000;83(02):167–76.
Maeda H, Kuwahara H, Ichimura Y, Ohtsuki M, Kurakata S, Shiraishi A. TGF-beta enhances macrophage ability to produce IL-10 in normal and tumor-bearing mice. J Immunol. 1995;155(10):4926.
Massagué J. TGF [beta] in cancer. Cell. 2008;134(2):215–30.
Maeda H, Shiraishi A. TGF-beta contributes to the shift toward Th2-type responses through direct and IL-10-mediated pathways in tumor-bearing mice. J Immunol. 1996;156(1):73.
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Maroof, H., Hassan, Z.M., Mobarez, A.M. et al. Lactobacillus acidophilus Could Modulate the Immune Response Against Breast Cancer in Murine Model. J Clin Immunol 32, 1353–1359 (2012). https://doi.org/10.1007/s10875-012-9708-x
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DOI: https://doi.org/10.1007/s10875-012-9708-x