Possible Effects of Toxoplasma Gondii Infection on Breast Cancer Through Affecting Programmed Death-1 Genes

Omar Abdulraheem Ali (1), Amal khudair Khalaf (2)
(1) Department of Microbiology, College of Medicine, University of Thi-Qar, Iraq, Iraq,
(2) a:1:{s:5:"en_US";s:17:"Thiqar University";}, Iraq

Abstract

Background: This study aimed to evaluate the possible effects of Toxoplasma gondii infection on breast cancer through affecting the  serum and expression gene level of programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1)  in breast cancer patients from Thi-qar province, Iraq.


Methods: This case-control study was involved 150 patients suffering from breast cancer (BC) who were referring to general hospitals of Thi-Qar province between July to September 2023 and 150 healthy patients (non-BC). Enzyme-linked immunosorbent test (ELISA) kit was used to evaluate the anti-Toxoplasma IgG and the serum level of PD-1 and PDL-1. Furthermore, the expression level of PD-1 and PDL-1 was measured through Real-time PCR.


Results: Among 150 breast cancer patients, 71 patients (47.3%) and 25 (16.6%) of healthy subjects exhibited seropositivity for anti-T. gondii IgG antibodies, resepectively. We found that the serum level and the gene expression level of PD-1 and PDL-1 were significantly higher among BC patients seropositive for T. gondii compared with BC patients who were seronegative for T. gondii antibodies (p<0.05).


Conclusion: These results indicated that T. gondii may play a role in the occurrence and even progression of cancer probably by elevating levels of PD-1 and PDL-1 genes. However, further studies are required to confirm these findings.

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References

Saadatnia G, Golkar M. A review on human toxoplasmosis. Scand J Infect Dis. 2012 Nov;44(11):805-14. doi: 10.3109/00365548.2012.693197.

Mukhopadhyay D, Arranz-Solís D, Saeij JPJ. Influence of the Host and Parasite Strain on the Immune Response During Toxoplasma Infection. Front Cell Infect Microbiol. 2020 Oct 15;10:580425. doi: 10.3389/fcimb.2020.580425.

Rostami A, Riahi SM, Contopoulos-Ioannidis DG, Gamble HR, Fakhri Y, Shiadeh MN, Foroutan M, Behniafar H, Taghipour A, Maldonado YA, Mokdad AH, Gasser RB. Acute Toxoplasma infection in pregnant women worldwide: A systematic review and meta-analysis. PLoS Negl Trop Dis. 2019 Oct 14;13(10):e0007807. doi: 10.1371/journal.pntd.0007807.

Molan A, Nosaka K, Hunter M, Wang W. Global status of Toxoplasma gondii infection: systematic review and prevalence snapshots. Trop Biomed. 2019 Dec 1;36(4):898-925

Molan A, Nosaka K, Hunter M, Wang W. Global status of Toxoplasma gondii infection: systematic review and prevalence snapshots. Trop Biomed. 2019 Dec 1;36(4):898-925.

Anvari D, Sharif M, Sarvi S, Aghayan SA, Gholami S, Pagheh AS, Hosseini SA, Saberi R, Chegeni TN, Hosseininejad Z, Daryani A. Seroprevalence of Toxoplasma gondii infection in cancer patients: A systematic review and meta-analysis. Microb Pathog. 2019 Apr;129:30-42. doi: 10.1016/j.micpath.2019.01.040.

Zhang N, Tu J, Wang X, Chu Q. Programmed cell death-1/programmed cell death ligand-1 checkpoint inhibitors: differences in mechanism of action. Immunotherapy. 2019 Apr;11(5):429-441. doi: 10.2217/imt-2018-0110.

Kornepati AVR, Vadlamudi RK, Curiel TJ. Programmed death ligand 1 signals in cancer cells. Nat Rev Cancer. 2022 Mar;22(3):174-189. doi: 10.1038/s41568-021-00431-4. Epub 2022 Jan 14. Erratum in: Nat Rev Cancer. 2022 Mar;22(3):190. doi: 10.1038/s41568-022-00445-6.

Khan IA, Ouellette C, Chen K, Moretto M. Toxoplasma: Immunity and Pathogenesis. Curr Clin Microbiol Rep. 2019 Mar;6(1):44-50. doi: 10.1007/s40588-019-0114-5.

Gocher AM, Workman CJ, Vignali DAA. Interferon-γ: teammate or opponent in the tumour microenvironment? Nat Rev Immunol. 2022 Mar;22(3):158-172. doi: 10.1038/s41577-021-00566-3.

Ajoedi A, Al Azhar M, Nadliroh S, Hartini S, Andalusia R, Witarto AB. The mRNA expression profile of PD-1 and PD-L1 in peripheral blood of colorectal cancer patients. Indonesian Journal of Cancer. 2019 Oct 16;13(3):80-5. https://doi.org/10.33371/ijoc.v13i3.670.

Fisch D, Clough B, Frickel EM. Human immunity to Toxoplasma gondii. PLoS Pathog. 2019 Dec 12;15(12):e1008097. doi: 10.1371/journal.ppat.1008097.

Caner A. Toxoplasma gondii could have a possible role in the cancer mechanism by modulating the host's cell response. Acta Trop. 2021 Aug;220:105966. doi: 10.1016/j.actatropica.2021.105966.

Azab Hameed F, Khalaf AK. The effect of infection with Toxoplasma gondii in inducing interferon-gamma in breast cancer patients. Arch Razi Inst. 2024 Feb 1;79(1):138-143. doi: 10.32592/ARI.2024.79.1.138.

Ishida Y, Agata Y, Shibahara K, Honjo T. Induced expression of PD-1, a novel member of the immunoglobulin gene superfamily, upon programmed cell death. EMBO J. 1992 Nov;11(11):3887-95. doi: 10.1002/j.1460-2075.1992.tb05481.x.

Syn NL, Teng MWL, Mok TSK, Soo RA. De-novo and acquired resistance to immune checkpoint targeting. Lancet Oncol. 2017 Dec;18(12):e731-e741. doi: 10.1016/S1470-2045(17)30607-1. PMID: 29208439.

Francisco LM, Salinas VH, Brown KE, Vanguri VK, Freeman GJ, Kuchroo VK, Sharpe AH. PD-L1 regulates the development, maintenance, and function of induced regulatory T cells. J Exp Med. 2009 Dec 21;206(13):3015-29. doi: 10.1084/jem.20090847.

Kalim M, Iqbal Khan MS, Zhan J. Programmed cell death ligand-1: A dynamic immune checkpoint in cancer therapy. Chem Biol Drug Des. 2020 Jun;95(6):552-566. doi: 10.1111/cbdd.13677.

Al-Muskakeh, M. K., Yaseen, A. N., & Aldabagh, M. A. (2022). Assessment of Soluble PD-1 and PD-L1 in Iraqi Women Patients with Breast Cancer with Toxoplasmosis. Indian Journal of Forensic Medicine & Toxicology, 16(1): 1395-1404. https://doi.org/10.37506/ijfmt.v16i1.17692

Sadoon MM, Khalaf AK. Toxoplasma Gondii Related Programmed Cell Death (Pd1 and Pd-L1) in Patients with Diabetes Mellitus. University of Thi-Qar Journal of Medicine, 2023; 26(2): 313-319.

Atwan FK, Ali WR, Ghazi HF. An Essential Role of PD-1/PDL-1 In Placental of Aborted Women With Toxoplasmosis, Annals of Tropical Medicine and Public Health 2021; 24:570-576. http://dx.doi.org/10.36295/ASRO.2021.24603

Xiao J, Li Y, Rowley T, Huang J, Yolken RH, Viscidi RP. Immunotherapy targeting the PD-1 pathway alleviates neuroinflammation caused by chronic Toxoplasma infection. Sci Rep. 2023 Jan 23;13(1):1288. doi: 10.1038/s41598-023-28322-8.

Fife BT, Pauken KE. The role of the PD-1 pathway in autoimmunity and peripheral tolerance. Ann N Y Acad Sci. 2011 Jan;1217:45-59. doi: 10.1111/j.1749-6632.2010.05919.x.

Saçar MD, Bağcı C, Allmer J. Computational prediction of microRNAs from Toxoplasma gondii potentially regulating the hosts' gene expression. Genomics Proteomics Bioinformatics. 2014 Oct;12(5):228-38. doi: 10.1016/j.gpb.2014.09.002.

Thirugnanam S, Rout N, Gnanasekar M. Possible role of Toxoplasma gondii in brain cancer through modulation of host microRNAs. Infect Agent Cancer. 2013 Feb 8;8(1):8. doi: 10.1186/1750-9378-8-8.

He JJ, Ma J, Wang JL, Xu MJ, Zhu XQ. Analysis of miRNA expression profiling in mouse spleen affected by acute Toxoplasma gondii infection. Infect Genet Evol. 2016 Jan;37:137-42. doi: 10.1016/j.meegid.2015.11.005.

Assim MM, Saheb EJ. Serum Levels of Il-12 and Il-23 in Breast Cancer Patients Infected with Toxoplasma gondii: A Case-Control Study. Iran J Parasitol. 2020 Oct-Dec;15(4):466-474. doi: 10.18502/ijpa.v15i4.4850.

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 Jan;35(1):1-16. doi: 10.1089/jir.2014.0026.

Ye HM, Lu MJ, Liu Q, Lin Y, Tang LY, Ren ZF. Beneficial Effect of Toxoplasma gondii Infection on the Prognosis of Breast Cancer Was Modified by Cytokines. Clin Epidemiol. 2023 Apr 24;15:469-481. doi: 10.2147/CLEP.S408182.

Authors

Omar Abdulraheem Ali
Amal khudair Khalaf
akkhalaf99@gmail.com (Primary Contact)
1.
Ali OA, khudair Khalaf A. Possible Effects of Toxoplasma Gondii Infection on Breast Cancer Through Affecting Programmed Death-1 Genes. Arch Breast Cancer [Internet]. [cited 2024 Oct. 7];11(4). Available from: https://archbreastcancer.com/index.php/abc/article/view/991

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