Low-molecular-weight polysaccharides from Agaricus blazei Murrill modulate the Th1 response in cancer immunity

Jiang,Liyan; Yu,Zhipu; Lin,Yu; Cui,Liran; Yao,Shujuan; Lv,Liyan; Liu,Jicheng

doi:10.3892/ol.2018.7794

Low-molecular-weight polysaccharides from Agaricus blazei Murrill modulate the Th1 response in cancer immunity

Authors:
- Liyan Jiang
- Zhipu Yu
- Yu Lin
- Liran Cui
- Shujuan Yao
- Liyan Lv
- Jicheng Liu
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Affiliations: Department of Pathogen Biology, Qiqihar Medical University, Qiqihar, Heilongjiang 161006, P.R. China, Department of Medical Research, The Second Affiliated Hospital, Qiqihar Medical University, Qiqihar, Heilongjiang 161006, P.R. China , Department of Pharmacology, Qiqihar Medical University, Qiqihar, Heilongjiang 161006, P.R. China, Department of Medical Research, The First Affiliated Hospital, Qiqihar Medical University, Qiqihar, Heilongjiang 161041, P.R. China
Published online on: January 15, 2018 https://doi.org/10.3892/ol.2018.7794
Pages: 3429-3436
Copyright: © Jiang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

To assess the effect of low-molecular-weight polysaccharides from Agaricus blazei Murrill (ABP‑AW1) as an immunoadjuvant therapy for type 1 T‑helper (Th1) responses in tumorigenesis, C57BL/6 mice were inoculated subcutaneously with ovalbumin (E.G7‑OVA). After 3, 10 and 17 days, the mice were immunized with PBS, OVA alone, or OVA and ABP‑AW1, at low (50 µg), intermediate (100 µg) or high (200 µg) doses. Tumor growth was examined and compared among the groups, as were the following parameters: Splenocyte viability/proliferation, peripheral blood CD4+/CD8+ T cell ratio, serum OVA‑specific IgG1 and IgG2b, secretion of interleukin (IL)‑2 and interferon (IFN)‑γ, and IFN‑γ production on a single cell level from cultured splenocytes. Tumor growth in mice treated with OVA and ABP‑AW1 (100 or 200 µg) was significantly slower, compared with in the other groups at the same time-points. OVA with 100 or 200 µg ABP‑AW1 was associated with a higher number of total splenocytes, a higher ratio of peripheral blood CD4+/CD8+ T‑lymphocytes, higher serum levels of OVA‑specific Th1‑type antibody IgG2b and greater secretion of the Th1 cytokines IL‑1 and IFN‑γ from splenocytes. ABP‑AW1 is a promising immunoadjuvant therapy candidate, due to its ability to boost the Th1 immune response when co‑administered with a cancer vaccine intended to inhibit cancer progression.

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1	Arruebo M, Vilaboa N, Sáez-Gutierrez B, Lambea J, Tres A, Valladares M and González-Fernández A: Assessment of the evolution of cancer treatment therapies. Cancers. 3:3279–3330. 2011. View Article : Google Scholar : PubMed/NCBI
2	Farkona S, Diamandis EP and Blasutig IM: Cancer immunotherapy: The beginning of the end of cancer? BMC Med. 14:732016. View Article : Google Scholar : PubMed/NCBI
3	Coley WB: The treatment of malignant tumors by repeated inoculations of erysipelas. With a report of ten original cases. 1893. Clin Orthop Relat Res. 3–11. 1991.PubMed/NCBI
4	Parish CR: Cancer immunotherapy: The past, the present and the future. Immunol Cell Biol. 81:106–113. 2003. View Article : Google Scholar : PubMed/NCBI
5	Wiemann B and Starnes CO: Coley's toxins, tumor necrosis factor and cancer research: A historical perspective. Pharmacol Ther. 64:529–564. 1994. View Article : Google Scholar : PubMed/NCBI
6	Drake CG, Lipson EJ and Brahmer JR: Breathing new life into immunotherapy: Review of melanoma, lung and kidney cancer. Nat Rev Clin Oncol. 11:24–37. 2014. View Article : Google Scholar : PubMed/NCBI
7	Mellman I, Coukos G and Dranoff G: Cancer immunotherapy comes of age. Nature. 480:480–489. 2011. View Article : Google Scholar : PubMed/NCBI
8	Guo C, Manjili MH, Subjeck JR, Sarkar D, Fisher PB and Wang XY: Therapeutic cancer vaccines: Past, present, and future. Adv Cancer Res. 119:421–475. 2013. View Article : Google Scholar : PubMed/NCBI
9	Buonaguro L, Petrizzo A, Tornesello ML and Buonaguro FM: Translating tumor antigens into cancer vaccines. Clin Vaccine Immunol. 18:23–34. 2011. View Article : Google Scholar : PubMed/NCBI
10	Rajput ZI, Hu SH, Xiao CW and Arijo AG: Adjuvant effects of saponins on animal immune responses. J Zhejiang Univ Sci B. 8:153–161. 2007. View Article : Google Scholar : PubMed/NCBI
11	Jones DE, Palmer JM, Burt AD, Walker C, Robe AJ and Kirby JA: Bacterial motif DNA as an adjuvant for the breakdown of immune self-tolerance to pyruvate dehydrogenase complex. Hepatology. 36:679–686. 2002. View Article : Google Scholar : PubMed/NCBI
12	Tovey MG and Lallemand C: Adjuvant activity of cytokines. Methods Mol Biol. 626:287–309. 2010. View Article : Google Scholar : PubMed/NCBI
13	Tefit JN and Serra V: Outlining novel cellular adjuvant products for therapeutic vaccines against cancer. Expert Rev Vaccines. 10:1207–1220. 2011. View Article : Google Scholar : PubMed/NCBI
14	Petrovsky N and Aguilar JC: Vaccine adjuvants: Current state and future trends. Immunol Cell Biol. 82:488–496. 2004. View Article : Google Scholar : PubMed/NCBI
15	Schietinger A, Philip M, Liu RB, Schreiber K and Schreiber H: Bystander killing of cancer requires the cooperation of CD4(+) and CD8(+) T cells during the effector phase. J Exp Med. 207:2469–2477. 2010. View Article : Google Scholar : PubMed/NCBI
16	Kim HJ and Cantor H: CD4 T-cell subsets and tumor immunity: The helpful and the not-so-helpful. Cancer Immunol Res. 2:91–98. 2014. View Article : Google Scholar : PubMed/NCBI
17	Ramberg JE, Nelson ED and Sinnott RA: Immunomodulatory dietary polysaccharides: A systematic review of the literature. Nutr J. 9:542010. View Article : Google Scholar : PubMed/NCBI
18	Cui L, Sun Y, Xu H, Cong H and Liu J: A polysaccharide isolated from Agaricus blazei Murill (ABP-AW1) as a potential Th1 immunity-stimulating adjuvant. Oncol Lett. 6:1039–1044. 2013. View Article : Google Scholar : PubMed/NCBI
19	Liu J and Sun Y: Structural analysis of an alkali-extractable and water-soluble polysaccharide (ABP-AW1) from the fruiting bodies of Agaricus blazei Murill. Carbohydrate Polymers. 86:429–432. 2011. View Article : Google Scholar
20	Hartmann G, Marschner A, Viveros PR, Stahl-Hennig C, Eisenblatter M, Suh YS, Endres S, Tenner-Racz K, Uberla K, Racz P, et al: CpG oligonucleotides induce strong humoral but only weak CD4⁺ T cell responses to protein antigens in rhesus macaques in vivo. Vaccine. 23:3310–3317. 2005. View Article : Google Scholar : PubMed/NCBI
21	Sjölander A, van't Land B and Bengtsson Lövgren K: Iscoms containing purified Quillaja saponins upregulate both Th1-like and Th2-like immune responses. Cell Immunol. 177:69–76. 1997. View Article : Google Scholar : PubMed/NCBI
22	Kawase O, Goo YK, Jujo H, Nishikawa Y and Xuan X: Starfish, Asterias amurensis and Asterina pectinifera, as potential sources of Th1 immunity-stimulating adjuvants. J Vet Med Sci. 73:227–229. 2011. View Article : Google Scholar : PubMed/NCBI
23	Mountford AP, Fisher A and Wilson RA: The profile of IgG1 and IgG2a antibody responses in mice exposed to Schistosoma mansoni. Parasite Immunol. 16:521–527. 1994. View Article : Google Scholar : PubMed/NCBI
24	Hanahan D and Weinberg RA: The hallmarks of cancer. Cell. 100:57–70. 2000. View Article : Google Scholar : PubMed/NCBI
25	Hanahan D and Weinberg RA: Hallmarks of cancer: The next generation. Cell. 144:646–674. 2011. View Article : Google Scholar : PubMed/NCBI
26	Escors D: Tumour immunogenicity, antigen presentation and immunological barriers in cancer immunotherapy. New J Sci. 2014:7345152014. View Article : Google Scholar : PubMed/NCBI
27	Dubensky TW Jr and Reed SG: Adjuvants for cancer vaccines. Semin Immunol. 22:155–161. 2010. View Article : Google Scholar : PubMed/NCBI
28	Knutson KL and Disis ML: Tumor antigen-specific T helper cells in cancer immunity and immunotherapy. Cancer Immunol Immunother. 54:721–728. 2005. View Article : Google Scholar : PubMed/NCBI
29	Romagnani S: T-cell subsets (Th1 versus Th2). Ann Allergy Asthma Immunol. 85:9–18. 2000. View Article : Google Scholar : PubMed/NCBI
30	Wang X and Meng D: Innate endogenous adjuvants prime to desirable immune responses via mucosal routes. Protein Cell. 6:170–184. 2015. View Article : Google Scholar : PubMed/NCBI
31	Sun Y, Liu J, Yu H and Gong C: Isolation and evaluation of immunological adjuvant activities of saponins from the roots of Pulsatilla chinensis with less adverse reactions. Int Immunopharmacol. 10:584–590. 2010. View Article : Google Scholar : PubMed/NCBI
32	Shurin MR, Lu L, Kalinski P, Stewart-Akers AM and Lotze MT: Th1/Th2 balance in cancer, transplantation and pregnancy. Springer Semin Immunopathol. 21:339–359. 1999. View Article : Google Scholar : PubMed/NCBI
33	Zamarron BF and Chen W: Dual roles of immune cells and their factors in cancer development and progression. Int J Biol Sci. 7:651–658. 2011. View Article : Google Scholar : PubMed/NCBI
34	Lee PP, Zeng D, McCaulay AE, Chen YF, Geiler C, Umetsu DT and Chao NJ: T helper 2-dominant antilymphoma immune response is associated with fatal outcome. Blood. 90:1611–1617. 1997.PubMed/NCBI
35	Hu HM, Urba WJ and Fox BA: Gene-modified tumor vaccine with therapeutic potential shifts tumor-specific T cell response from a type 2 to a type 1 cytokine profile. J Immunol. 161:3033–3041. 1998.PubMed/NCBI
36	Ghosh P, Komschlies KL, Cippitelli M, Longo DL, Subleski J, Ye J, Sica A, Young HA, Wiltrout RH and Ochoa AC: Gradual loss of T-helper 1 populations in spleen of mice during progressive tumor growth. J Natl Cancer Inst. 87:1478–1483. 1995. View Article : Google Scholar : PubMed/NCBI
37	Tzianabos AO: Polysaccharide immunomodulators as therapeutic agents: Structural aspects and biologic function. Clin Microbiol Rev. 13:523–533. 2000. View Article : Google Scholar : PubMed/NCBI
38	Honda-Okubo Y, Saade F and Petrovsky N: Advax^™, a polysaccharide adjuvant derived from delta inulin, provides improved influenza vaccine protection through broad-based enhancement of adaptive immune responses. Vaccine. 30:5373–5381. 2012. View Article : Google Scholar : PubMed/NCBI
39	Saade F, Honda-Okubo Y, Trec S and Petrovsky N: A novel hepatitis B vaccine containing Advax^™, a polysaccharide adjuvant derived from delta inulin, induces robust humoral and cellular immunity with minimal reactogenicity in preclinical testing. Vaccine. 31:1999–2007. 2013. View Article : Google Scholar : PubMed/NCBI
40	Blankenstein T, Coulie PG, Gilboa E and Jaffee EM: The determinants of tumour immunogenicity. Nat Rev Cancer. 12:307–313. 2012. View Article : Google Scholar : PubMed/NCBI
41	Chaplin DD: Overview of the immune response. J Allergy Clin Immunol. 125 Suppl 2:S3–S23. 2010. View Article : Google Scholar : PubMed/NCBI
42	Serrano-Villar S, Sainz T, Lee SA, Hunt PW, Sinclair E, Shacklett BL, Ferre AL, Hayes TL, Somsouk M, Hsue PY, et al: HIV-infected individuals with low CD4/CD8 ratio despite effective antiretroviral therapy exhibit altered T cell subsets, heightened CD8⁺ T cell activation, and increased risk of non-AIDS morbidity and mortality. PLoS Pathog. 10:e10040782014. View Article : Google Scholar : PubMed/NCBI