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Immunization with Hydatid Cyst Wall Antigens Can Inhibit Breast Cancer through Changes in Serum Levels of Th1/Th2 Cytokines
Abstract
Background: Hydatid cysts are the larval stage of Echinococcus granulosus, which lead to humoral and cellular immune responses in hosts. Such immune responses play a key role in the inhibition of tumor growth and cancers. To test this hypothesis, it was attempted not only to examine the changes in serum level of some Th1 and Th2 cytokines but also to find relationships between the cytokines and cancer in 4T1 breast cancer‑bearing mice immunized with hydatid cyst wall (HCW) antigens.
Methods: Six to eight‑week‑old Balb/c female mice were immunized with alum, PBS and HCW antigens, including crude extract of HCW (laminated layer) 28 and 27 kDa protein bands (upper and lower bands) and then challenged with 4T1 breast cancer cells. The amounts of IL2, TNF‑α, IFN‑γ (Th1 cytokines), and IL4 (Th2 cytokine) were estimated using ELISA. Correlations between these cytokines and cancer parameters (tumor growth, metastasis, and survival) were determined by Pearson’s correlation coefficients.
Results: Overall, HCW antigens increased the amounts of IL2, TNF‑α, IFN‑γ, and IL4. Pearson’s correlation coefficients indicated reverse relationships between changes in amounts of these cytokines and tumor growth/ metastasis. However, except for IL‑4, all cytokines had a direct relationship with mouse survival.
Conclusions: The results of this study indicated that the inhibition of breast tumor growth and metastasis and improvement of survival in 4T1 mice immunized with HCW antigens, especially laminated layer and 27 kDa protein band can occur through a rise in the levels of cytokines.
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WHO, cancer, Early Diagnosis and Screening, Breast cancer.
Available from: https://www.who.int/cancer/prevention/diagnosisscreening/breast-cancer/en/. [Last accessed on 2019 Nov 29].
Jiwa M, Long A, Shaw T, Pagey G, Halkett G, Pillai V, et al. The
management of acute adverse effects of breast cancer treatment
in general practice: A video‑vignette study. J Med Internet Res
;16:e204.
Fann JR, Thomas‑Rich AM, Katon WJ, Cowley D, Pepping M,
McGregor BA, et al. Major depression after breast cancer:
A review of epidemiology and treatment. Gen Hosp Psychiatry
;30:112‑26.
Navrozoglou I, Vrekoussis T, Kontostolis E, Dousias V,
Zervoudis S, Stathopoulos E, et al. Breast cancer during
pregnancy: A mini‑review. Eur J Surg Oncol 2008;34:837‑43.
Hackl H, Charoentong P, Finotello F, Trajanoski Z.
Computational genomics tools for dissecting tumour–immune
cell interactions. Nat Rev Genet 2016;17:441‑58.
Schumacher TN, Schreiber RD. Neoantigens in cancer
immunotherapy. Science 2015;348:69‑74.
Backert L, Kohlbacher O. Immunoinformatics and epitope prediction
in the age of genomic medicine. Genome Med 2015;7:119.
Mocellin S. Cancer vaccines: The challenge of developing an
ideal tumor killing system. Front Biosci 2005;10:2285‑305.
Darani HY, Shirzad H, Mansoori F, Zabardast N,
Mahmoodzadeh M. Effects of Toxoplasma gondii and Toxocara
canis antigens on WEHI‑164 fibrosarcoma growth in a mouse
model. Korean J Parasitol 2009;47:175‑7.
Kim JO, Jung SS, Kim SY, Kim TY, Shin DW, Lee JH, et al.
Inhibition of Lewis lung carcinoma growth by Toxoplasma
gondii through induction of Th1 immune responses and
inhibition of angiogenesis. J Korean Med Sci 2007;22:S38‑46.
Kallinikova V, Borisova E, Pakhorukova L, Ogloblina T,
Batmonkh T, Kravtsov E, et al. Immunization against Trypanosoma
cruzi and tumor growth in mice. Med Parazitol (Mosk) 2006;4:9‑12.
Kinnamon KE, Poon BT, Hanson WL, Waits VB. Activity of
anticancer compounds against Trypanosoma cruzi‑infected mice.
Am J Trop Med Hyg 1998;58:804‑6.
Batmonkh Z, Kallinikova V, Pakhorukova L, Kravtsov E,
Karpenko L, Dalin M. In vivo anticancer activity of lysates from
Trypanosoma cruzi of different genetic groups. Bull Exp Biol
Med 2006;142:470‑3.
Daneshpour S, Kefayat AH, Mofid MR, Rad SR, Darani HY.
Effect of hydatid cyst fluid antigens on induction of apoptosis on
breast cancer cells. Adv Biomed Res 2019;8:27.
Chookami MB, Sharafi SM, Sefiddashti RR, Jafari R,
Bahadoran M, Pestechian N, et al. Effect of two hydatid cyst
antigens on the growth of melanoma cancer in C57/black mice.
J Parasit Dis 2016;40:1170‑3.
Rostami SR, Daneshpour S, Mofid M, Andalib A,
Eskandariyan A, Yousofi HD. Effect of hydatid cyst antigens on
inhibition of melanoma cancer growth in mouse model. Cell Mol
Biol (Noisy‑le‑grand) 2018;64:1‑5.
Pakala T, Molina M, Wu GY. Hepatic Echinococcal cysts:
A review. J Clin Transl Hepatol 2016;4:39‑46.
Tamarozzi F, Mariconti M, Neumayr A, Brunetti E. The
intermediate host immune response in cystic echinococcosis.
Parasite Immunol 2016;38:170‑81.
Golzari SE, Sokouti M. Pericyst: The outermost layer of hydatid
cyst. World J Gastroenterol 2014;20:1377‑8.
Sefiddashti RR, Sharafi SM, Ebrahimi SA, Akhlaghi L,
Moosavi A, Eskandarian A, et al. Antibody response to glycan
antigens of hydatid cyst fluid, laminated layer and protoscolex of
Echinococcus granulosus. Med J Islam Repub Iran 2017;31:12.
Sefiddashti RR, Sharafi SM, Ebrahimi SA, Akhlaghi L,
Moosavi A, Eskandarian A, et al. A 53 KDa glycan antigen of
hydatid cyst wall may involve in evasion from host immune
system. Adv Biomed Res 2018;7:82.
Kapczuk P, Kosik‑Bogacka D, Łanocha‑Arendarczyk N,
Gutowska I, Kupnicka P, Chlubek D, et al. Selected molecular
mechanisms involved in the parasite–host system hymenolepis
diminuta–rattus norvegicus. Int J Mol Sci 2018;19:2435.
Hegewald J, Gantin RG, Lechner CJ, Huang X, Agosssou A,
Agbeko YF, et al. Cellular cytokine and chemokine responses
to parasite antigens and fungus and mite allergens in
children co‑infected with helminthes and protozoa parasites.
J Inflamm (Lond) 2015;12:5.
Romagnani S. Type 1 T helper and type 2 T helper cells:
Functions, regulation and role in protection and disease. Int J
Clin Lab Res 1992;21:152‑8.
Zhang W, Ross AG, McManus DP. Mechanisms of immunity
in hydatid disease: Implications for vaccine development.
J Immunol 2008;181:6679‑85.
Sharafi SM, Rafiei R, Rafiei R, Hadipour M, Shirzad H,
Khanahmad H, et al. A Nonglycosylated 27 kDa molecule as
common antigen between human breast cancer and Echinococcus
granulosus hydatid cyst wall. Adv Breast Cancer Res 2016;5:90‑5.
Sharafi SM, Shirzad H, Khanahmad H, Ataei B, Darani HY.
Monoclonal antibodies production against a 40KDa band of
hydatid cyst fluid. Recent Pat Biotechnol 2018;12:57‑64.
Rostami‑Rad S, Jafari R, Darani HY. Th1/Th2‑type cytokine
profile in C57 black mice inoculated with live Echinococcus
granulosus protoscolices. J Infect Public Health 2018;11:834‑9.
Mezioug D, Touil‑Boukoffa C. Cytokine profile in human
hydatidosis: Possible role in the immunosurveillance of patients
infected with Echinococcus granulosus. Parasite 2009;16:57‑64.
Walker WH II, Borniger JC, Zalenski AA, Muscarella SL,
Fitzgerald JA, Zhang N, et al. Mammary tumors induce central
pro‑inflammatory cytokine expression, but not behavioral deficits
in Balb/C mice. Sci Rep 2017;7:8152.
Condotta SA, Richer MJ. The immune battlefield: The impact of
inflammatory cytokines on CD8+ T‑cell immunity. PLoS Pathog
;13:e1006618.
Spiering MJ. Primer on the immune system. Alcohol Res
;37:171‑5.
Altun A, Saraydin SU, Soylu S, Inan DS, Yasti C, Ozdenkaya Y,
et al. Chemopreventive effects of hydatid disease on experimental
breast cancer. Asian Pac J Cancer Prev 2015;16:1391‑5.
Berriel E, Russo S, Monin L, Festari MF, Berois N,
Fernández G, et al. Antitumor activity of human hydatid cyst
fluid in a murine model of colon cancer. Scientific World Journal
;2013:230176.
Turhan N, Esendagli G, Ozkayar O, Tunali G, Sokmensuer C,
Abbasoglu O. Co-existence of E chinococcus granulosus infection
and cancer metastasis in the liver correlates with reduced Th1
immune responses. Parasite Immunol 2015;37:16‑22.
Chen L, He Z, Qin L, Li Q, Shi X, Zhao S, et al. Antitumor
effect of malaria parasite infection in a murine Lewis lung cancer
model through induction of innate and adaptive immunity. PLoS
One 2011;6:e24407.
Nicolini A, Carpi A, Rossi G. Cytokines in breast cancer.
Cytokine Growth Factor Rev 2006;17:325‑37.
García‑Tuñón I, Ricote M, Ruiz A, Fraile B, Paniagua R,
Royuela M. Influence of IFN‑gamma and its receptors in human
breast cancer. BMC Cancer 2007;7:158.
Esquivel‑Velázquez M, Ostoa‑Saloma P, Palacios‑Arreola MI,
Nava‑Castro KE, Castro JI, Morales‑Montor J. The role of
cytokines in breast cancer development and progression.
J Interferon Cytokine Res 2015;35:1‑16.
Nagai S, Toi M. Interleukin‑4 and breast cancer. Breast Cancer
;7:181‑6.
Ma Y, Ren Y, Dai Z‑J, Wu C‑J, Ji Y‑H, Xu J. IL‑6, IL‑8 and
TNF‑α levels correlate with disease stage in breast cancer
patients. Adv Clin Exp Med 2017;26:421‑6.
Gaggianesi M, Turdo A, Chinnici A, Lipari E, Apuzzo T,
Benfante A, et al. IL4 primes the dynamics of breast
cancer progression via DUSP4 inhibition. Cancer Res
;77:3268‑79.