Exploring the Potential of Echinococcus Granulosus Antigens in Immunotherapy for Cancer

Safa Ebran Safahi; Amin Ahmadi

doi:10.63053/ijhes.84

Authors

Safa Ebran Safahi Department of Basic Sciences, Faculty of Veterinary Medicine, Ardakan University, P.O. Box 184, Ardakan, Iran.
Amin Ahmadi Biology and Animal Reproduction Science Research Institute, Ardakan University, Ardakan, Iran https://orcid.org/0000-0002-3566-7134

DOI:

https://doi.org/10.63053/ijhes.84

Keywords:

Cancer; Echinococcus granulosus; Hydatid Cyst; Immunotherapy; Innate Immunity

Abstract

Background: Echinococcus granulosus, intrigues researchers due to its unique biology and immunogenicity. Recent studies show a negative relationship between echinococcosis incidence and cancer progression, emphasizing significant similarities between E. granulosus and cancer antigens. This article will review the anti-cancer effects of E. granulosus antigens and their application in cancer immunotherapy.

Main Body: It begins with an introduction, highlighting the significance of E. granulosus antigens in contemporary cancer treatment. Subsequently, an overview of hydatid cysts, the source of these antigens, elucidating their structure and immunogenic properties is provided. Our review extends to the interactions between echinococcosis and both the innate and acquired immune systems, shedding light on the mechanisms involved. We delve into the intriguing connections between echinococcosis and cancer, exploring the direct and indirect anti-cancer effects of these antigens and their potential in cancer immunotherapy. To offer a balanced perspective, we also weigh the pros and cons of using E. granulosus antigens in cancer therapy.

Conclusion: In conclusion, the promising attributes of E. granulosus antigens, as highlighted throughout this review, suggest a bright future for their utilization in cancer therapy. Their ability to trigger potent immune responses and target cancer cells holds great potential for the development of effective and tailored therapies, offering new hope for improved cancer treatment outcomes. Further research and clinical trials are needed to fully realize the potential of E. granulosus antigens in the field of cancer immunotherapy.

Author Biography

Amin Ahmadi, Biology and Animal Reproduction Science Research Institute, Ardakan University, Ardakan, Iran

*Correspondence Author: Dr. Amin Ahmadi

Assistant professor of the Veterinary Parasitology, Department of Basic Sciences, Faculty of Veterinary Medicine, Ardakan University, P.O. Box 184, Ardakan, Iran.

Head of Biology and Animal Reproduction Science Research Institute, Ardakan University, Ardakan, Iran.

References

- Ahmadi, A., F. Barekati, K. Amini, A. Rasooli and M. Mazrouei. 2022. The Role of Zoonotic Helminths in Causing Cancer. Zoonosis 2: 9-24.

- Ahmadi, A., M. Moazeni and M. Shaddel. 2020. Subcutaneous Hydatid Cyst in Laboratory Mice: Is it a Suitable Method for Evaluating Therapeutic Agents against Hydatid Cyst? Archives of Razi Institute 75: 75-81.

- Amri, M., D. Mezioug and C. Touil-Boukoffa. 2009. Involvement of IL-10 and IL-4 in evasion strategies of Echinococcus granulosus to host immune response. European cytokine network 20: 63-68.

- Asouli, A., S. Sadr, H. Mohebalian and H. Borji. 2023. Anti-Tumor Effect of Protoscolex Hydatid Cyst Somatic Antigen on Inhibition Cell Growth of K562. Acta parasitologica 68: 385-392.

- Badri-Chookami, M., S. M. Sharafi, R. Rafeie, M. Bahadoran, N. Pestechian and H. Yousofi-Darani. 2014. Effect of Alive Protoscoleces of Hydatid Cyst on the Growth of Melanoma Cells in Mouse Model. Journal of Isfahan Medical School 32: 486-492.

-Bakhtiar, N. M., A. Spotin, M. Mahami-Oskouei, E. Ahmadpour and A. Rostami. 2020. Recent advances on innate immune pathways related to host–parasite cross-talk in cystic and alveolar echinococcosis. Parasites & Vectors 13: 232.

-Basu, A., G. Ramamoorthi, G. Albert, C. Gallen, A. Beyer, C. Snyder, G. Koski, M. L. Disis, B. J. Czerniecki and K. Kodumudi. 2021. Differentiation and Regulation of TH Cells: A Balancing Act for Cancer Immunotherapy Frontiers in Immunology

- Benvenuto, M., C. Focaccetti, V. Izzi, L. Masuelli, A. Modesti and R. Bei. 2021. Tumor antigens heterogeneity and immune response-targeting neoantigens in breast cancer. Seminars in Cancer Biology 72: 65-75.

-Berois, N., A. Pittini and E. Osinaga. 2022. Targeting Tumor Glycans for Cancer Therapy: Successes, Limitations, and Perspectives. Cancers 14.

- Berriel, E., T. Freire, C. Chiale, E. Rodríguez, G. Morón, G. Fernández-Graña, M. Crispo, N. Berois and E. Osinaga. 2021. Human hydatid cyst fluid-induced therapeutic anti-cancer immune responses via NK1.1+ cell activation in mice. Cancer Immunology, Immunotherapy 70: 3617-3627.

- Berriel, E., S. Russo, L. Monin, M. F. Festari, N. Berois, G. Fernández, T. Freire and E. Osinaga. 2013. Antitumor activity of human hydatid cyst fluid in a murine model of colon cancer. TheScientificWorldJournal 2013: 230176.

- Cao, S., W. Gong, X. Zhang, M. Xu, Y. Wang, Y. Xu, J. Cao, Y. Shen and J. Chen. 2020. Arginase promotes immune evasion of Echinococcus granulosus in mice. Parasites & vectors 13: 49.

- Chen, J., W. Liao and H. Peng. 2022. Toxoplasma gondii infection possibly reverses host immunosuppression to restrain tumor growth Frontiers in Cellular and Infection Microbiology

- Daneshpour, S., M. Bahadoran, S. H. Hejazi, A. A. Eskandarian, M. Mahmoudzadeh and H. Y. Darani. 2016. Common antigens between hydatid cyst and cancers. Advanced biomedical research 5: 9.

- Daneshpour, S., A. H. Kefayat, M. R. Mofid, S. Rostami Rad and H. Yousofi Darani. 2019. Effect of Hydatid Cyst Fluid Antigens on Induction of Apoptosis on Breast Cancer Cells. Advanced biomedical research 8: 27.

- Darani, H. Y. and M. Yousefi. 2012. Parasites and cancers: parasite antigens as possible targets for cancer immunotherapy. Future oncology (London, England) 8: 1529-1535.

- GALINDO, M., M. J. GONZALEZ and N. GALANTI. 2002. Echinococcus granulosus protoscolex formation in natural infections. Biological Research 35: 365-371.

-Gessese, A. T. 2020. Review on Epidemiology and Public Health Significance of Hydatidosis. Veterinary medicine international 2020: 8859116.

- Golzari, S. E. J. and M. Sokouti. 2014. Pericyst: the outermost layer of hydatid cyst. World journal of gastroenterology. p. 1377-1378.

- Goussard, P., E. Eber, L. Mfingwana, P. Nel, P. Schubert, J. Janson, R. Pitcher and C. le Roux. 2022. Paediatric pulmonary echinococcosis: A neglected disease. Paediatric Respiratory Reviews 43: 11-23.

-Guan, W., X. Zhang, X. Wang, S. Lu, J. Yin and J. Zhang. 2019. Employing Parasite Against Cancer: A Lesson From the Canine Tapeworm Echinococcus Granulocus Frontiers in Pharmacology

- Hawash, Y. 2020. Parasitic Liver Diseases. In: Radu-Ionita F., Pyrsopoulos NT., Jinga M., Tintoiu IC., Sun Z., Bontas E, editors. Liver Diseases: A Multidisciplinary Textbook. Cham. Springer International Publishing. p. 161-172.

- Karadayi, S., S. Arslan, Z. Sumer, M. Turan, H. Sumer and K. Karadayi. 2013. Does hydatid disease have protective effects against lung cancer? Molecular Biology Reports 40: 4701-4704.

- Khalili, N., P. Iranpour, N. Khalili and S. Haseli. 2023. Hydatid Disease: A Pictorial Review of Uncommon Locations. Iranian Journal of Medical Sciences 48: 118-129.

-Khanfar, N. 2004. Hydatid disease: a review and update. Current Anaesthesia & Critical Care 15: 173-183.

- Kosmidis, C. S., K. Papadopoulos, C. M. Mystakidou, C. Sevva, C. Koulouris, N. Varsamis, S. Mantalovas, V. Lagopoulos, V. Magra, V. Theodorou, S. Ouzouni, N. Iason Katsios, P. Axi, K. Sapalidis and I. Kesisoglou. 2023. Giant Echinococcosis of the Liver with Suppuration: A Case Report and Review of the Literature. Medicina.

- Lau, C. M. and J. C. Sun. 2018. The widening spectrum of immunological memory. Current Opinion in Immunology 54: 42-49.

-Malik, A. A. and S. u. Bari. 2019. Biology of the Echinococcus. Human Abdominal Hydatidosis. Singapore. Springer Singapore. p. 1-13.

- Manterola, C., J. Rivadeneira, S. D. Pogue, C. Rojas, C. Manterola, J. Rivadeneira, S. D. Pogue and C. Rojas. 2023. Morphology of Echinococcus granulosus Protoscolex. International Journal of Morphology 41: 646-653.

-Milani, N., N. Majidi and L. Goshayeshi. 2021. Hydatid cyst of the liver with portal thrombosis: A case report. Authorea Preprints.

- Miles, D., H. Roché, M. Martin, T. J. Perren, D. A. Cameron, J. Glaspy, D. Dodwell, J. Parker, J. Mayordomo, A. Tres, J. L. Murray, N. K. Ibrahim and t. T. S. Group. 2011. Phase III Multicenter Clinical Trial of the Sialyl‐TN (STn)‐Keyhole Limpet Hemocyanin (KLH) Vaccine for Metastatic Breast Cancer. The Oncologist 16: 1092-1100.

- Moghaddam, S. M., S. Picot and E. Ahmadpour. 2019. Interactions between hydatid cyst and regulated cell death may provide new therapeutic opportunities. Parasite (Paris, France) 26: 70.

- Motran, C. C., L. F. Ambrosio, X. Volpini, D. P. Celias and L. Cervi. 2017. Dendritic cells and parasites: from recognition and activation to immune response instruction. Seminars in immunopathology 39: 199-213.

- Noya, V., S. Bay, M. F. Festari, E. P. García, E. Rodriguez, C. Chiale, C. Ganneau, F. Baleux, S. Astrada, M. Bollati-Fogolín, E. Osinaga and T. Freire. 2013. Mucin-like peptides from Echinococcus granulosus induce antitumor activity. International journal of oncology 43: 775-784.

-Organization, W. H. and others. 2011. Report of the WHO informal working group on cystic and alveolar echninococcosis surveillance, prevention and control, with the participation of the Food and Agriculture Organization of the United Nations and the World Organisation for Animal Health, 22-23.

-Ortona, E., P. Margutti, F. Delunardo, V. Nobili, E. Profumo, R. Riganò, B. Buttari, G. Carulli, A. Azzarà, A. Teggi, F. Bruschi and A. Siracusano. 2005. Screening of an Echinococcus granulosus cDNA library with IgG4 from patients with cystic echinococcosis identifies a new tegumental protein involved in the immune escape. Clinical and experimental immunology 142: 528-538.

- Ranasinghe, S. L., G. M. Boyle, K. Fischer, J. Potriquet, J. P. Mulvenna and D. P. McManus. 2018. Kunitz type protease inhibitor EgKI-1 from the canine tapeworm Echinococcus granulosus as a promising therapeutic against breast cancer. PloS one 13: e0200433.

- Ranasinghe, S. L. and D. P. McManus. 2018. Echinococcus granulosus: Cure for Cancer Revisited. Frontiers in medicine 5: 60.

-Rawat, S., R. Kumar, J. Raja, R. S. Singh and S. K. S. Thingnam. 2019. Pulmonary hydatid cyst: Review of literature. Journal of family medicine and primary care 8: 2774-2778.

- Ribeiro Franco, P. I., J. R. do Carmo Neto, M. P. Miguel, J. R. Machado and M. R. Nunes Celes. 2023. Cancer and Trypanosoma cruzi: Tumor induction or protection? Biochimie 207: 113-121.

- Sayek, I., M. B. Tirnaksiz and R. Dogan. 2004. Cystic Hydatid Disease: Current Trends in Diagnosis and Management. Surgery Today 34: 987-996.

-Shakibapour, M., A. Kefayat, M. Reza Mofid, B. Shojaie, F. Mohamadi, S. Maryam Sharafi, M. Mahmoudzadeh and H. Yousofi Darani. 2021. Anti-cancer immunoprotective effects of immunization with hydatid cyst wall antigens in a non-immunogenic and metastatic triple-negative murine mammary carcinoma model. International Immunopharmacology 99: 107955.

- Sharafi, S. M., R. Rafiei, R. Rafiei, M. Hadipour, H. Shirzad, H. Khanahmad and H. Y. Darani. 2016. A Nonglycosylated 27 KDa Molecule as Common Antigen between Human Breast Cancer and Echinococcus granulosus Hydatid Cyst Wall. Advances in Breast Cancer Research 05No.02: 6.

- Shepherd, J. C., A. Aitken and D. P. McManus. 1991. A protein secreted in vivo by Echinococcus granulosus inhibits elastase activity and neutrophil chemotaxis. Molecular and Biochemical Parasitology 44: 81-90.

- Shooraj, M., E. Hajipour and S. A. Mahdavi. 2022. Immunological Examination of Echinococcus granulosus as a Candidate for Cancer Treatment and Vaccine Development: A Review Study TT -. mazu-tbsrj 4: 0.

- Siracusano, A., F. Delunardo, A. Teggi and E. Ortona. 2012. Host-parasite relationship in cystic echinococcosis: an evolving story. Clinical & developmental immunology 2012: 639362.

- Sung, H., J. Ferlay, R. L. Siegel, M. Laversanne, I. Soerjomataram, A. Jemal and F. Bray. 2021. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: A Cancer Journal for Clinicians 71: 209-249.

- Taefehshokr, N., B. Baradaran, A. Baghbanzadeh and S. Taefehshokr. 2020. Promising approaches in cancer immunotherapy. Immunobiology 225: 151875.

-Tez, S. and M. Tez. 2015. Echinococcus and cancer: unsolved mystery. Parasite immunology. p. 426.

- Turhan, N., G. Esendagli, O. Ozkayar, G. Tunali, C. Sokmensuer and O. Abbasoglu. 2015. Co-existence of Echinococcus granulosus infection and cancer metastasis in the liver correlates with reduced Th1 immune responses. Parasite Immunology 37: 16-22.

-Veríssimo, C. D. M., C. Graeff-Teixeira, M. K. Jones and A. L. Morassutti. 2019. Glycans in the roles of parasitological diagnosis and host-parasite interplay. Parasitology 146: 1217-1232.

- Wu, L., S. Saxena, M. Awaji and R. K. Singh. 2019. Tumor-Associated Neutrophils in Cancer: Going Pro. Cancers.

-Yong, W. K., D. D. Heath and T. Savage. 1979. Possible antigenic similarity between pulmonary carcinoma and cysts of Echinococcus granulosus. British medical journal 1: 1463-1464.

- Zhang, W. and D. P. McManus. 2006. Recent advances in the immunology and diagnosis of echinococcosis. FEMS Immunology & Medical Microbiology 47: 24-41.

- Zhang, X., W. Gong, C. Duan, H. Cai, Y. Shen and J. Cao. 2022. Echinococcus granulosus Protoscoleces-Derived Exosome-like Vesicles and Egr-miR-277a-3p Promote Dendritic Cell Maturation and Differentiation. Cells.

- Zhang, Y., L. Sun, C. Lei, W. Li, J. Han, J. Zhang and Y. Zhang. 2022. A Sweet Warning: Mucin-Type O-Glycans in Cancer. Cells.