Blockade of LIRs as a new approach for diagnostics and treatment of ATLL malignancy

Cover Page


Cite item

Full Text

Abstract

In the new world of medicine, one of the main concerns in the field of infectious diseases has been focused on Human T-cell Leukemia Virus type 1 (HTLV-1). During the infection, lymphocyte inhibitory receptors (LIRs) play a prominent role in the occurrence of adult T-cell leukemia/lymphoma (ATLL). These receptors include LAG3, PD-1, TIGIT, CD160, TIM3, and 2B4. First, we have collected all microarray information on the profile of HTLV-1 infected patients from the Gene Expression Omnibus (http://www.ncbi.nlm.gov/geo) database until March 2020, in order to identify the microarray related to evolutionary development of LTRs during various phases of HTLV-1 infection in human peripheral blood CD4+ T cells by searching for keywords such as “Human T-lymphotropic virus type I (HTLV-1)”, “Homo sapiens”, “ATLL”, and “Whole genome sequencing”. Considering the main goal of the study, we have only assessed data related to Homo sapiens particularly CD4+ T cell lineage from human subjects infected with HTLV-1. We evaluated these receptors in ATLL patients compared to healthy control (HC) individuals and HTLV-1 infected-asymptomatic carriers (ASCs). Out of all 18 identified records, we only selected and analyzed three studies: GSE19080, GSE33615, and GSE57259, which satisfied inclusion criteria with proper quality analysis of ATLL vs. normal, ATLL vs. asymptomatic carrier as well as asymptomatic carrier vs. normal. Unfortunately, we could not analyze various stages of ATLL malignancy (acute, lymphomatous, chronic and smoldering) in all included studies due to the lack of sufficient information. Finally, based on Benjamini–Hochberg False discovery rate (FDR), the differentially expressed genes (DEGs) were selected for several categories. Hence, for the first time we demonstrated that the expression rate of LIRs in ATLL group was higher than either in asymptomatic carrier or healthy donor groups. As a conclusion, it seems that the blockade of LIRs has a pivotal role in diagnostics and treatment of ATLL malignancy.

About the authors

M. Keikha

Mashhad University of Medical Sciences

Email: masoud.keykha90@gmail.com
ORCID iD: 0000-0003-1208-8479

PhD, Department of Microbiology and Virology, Faculty of Medicine, Mashhad University Medical Sciences.

Mashhad.

Iran, Islamic Republic of

M. Karbalaei

Jiroft University of Medical Sciences

Author for correspondence.
Email: mohsen.karbalaei@jmu.ac.ir
ORCID iD: 0000-0001-9899-2885

Mohsen Karbalaei - PhD, Department of Microbiology and Virology, School of Medicine, Jiroft University of Medical Sciences.

Jiroft.

Phone: +98 913 193-36-12

Russian Federation

References

  1. Andrews L.P., Marciscano A.E., Drake C.G., Vignali D.A. LAG 3 (CD223) as a cancer immunotherapy target. Immun. Rev., 2017, vol. 276, no. 1, pp. 80–96. doi: 10.1111/imr.12519
  2. Bangham C.R. Human T cell leukemia virus type 1: persistence and pathogenesis. Annu. Rev. Immunol., 2018, vol. 36, pp. 43–71. doi: 10.1146/annurev-immunol-042617-053222
  3. Barta S.K., Zain J., MacFarlane A.W. 4th, Smith S.M., Ruan J., Fung H.C., Tan C.R., Yang Y., Alpaugh R.K., Dulaimi E., Ross E.A., Campbell K.S., Khan N., Siddharta R., Fowler N.H., Fisher R.I., Oki Y. Phase II study of the PD-1 inhibitor pembrolizumab for the treatment of relapsed or refractory mature T-cell lymphoma. Clin. Lymphoma Myeloma Leuk., 2019, vol. 19, no. 6, pp. 356–364.e3. doi: 10.1016/j.clml.2019.03.022
  4. Chibueze C.E., Yoshimitsu M., Arima N. CD160 expression defines a uniquely exhausted subset of T lymphocytes in HTLV-1 infection. Biochem. Biophys. Res. Commun., 2014, vol. 453, no. 3, pp. 379–384. doi: 10.1016/j.bbrc.2014.09.084
  5. Ezinne C.C., Yoshimitsu M., White Y., Arima N. HTLV-1 specific CD8+ T cell function augmented by blockade of 2B4/CD48 interaction in HTLV-1 infection. PloS One, 2014, vol. 9, no. 2: e87631. doi: 10.1371/journal.pone.0087631
  6. Feeney K., Kelly R., Lipton LR., Chao J., Acosta-Rivera M., Earle D., Lei M., Kollia G., Tebbutt N.C. CA224-060: a randomized, open label, phase II trial of relatlimab (anti-LAG-3) and nivolumab with chemotherapy versus nivolumab with chemotherapy as first-line treatment in patients with gastric or gastroesophageal junction adenocarcinoma. Am. J. Clin. Oncol., 2019, vol. 37, no. 15: TPS4143. doi: 10.1200/JCO.2019.37.15_suppl.TPS4143
  7. Futsch N., Prates G., Mahieux R., Casseb J., Dutartre H. Cytokine networks dysregulation during HTLV-1 infection and associated diseases. Viruses, 2018, vol. 10, no. 12: 691. doi: 10.3390/v10120691
  8. Ghazvini K., Youssefi M., Keikha M. Expression changes of cytotoxicity and apoptosis genes in HTLV-1-associated myelopathy/ tropical spastic paraparesis patients from the perspective of system virology. Access Microbiol., 2020, vol. 2, no. 3: acmi000088. doi: 10.1099/acmi.0.000088
  9. Hude I., Sasse S., Engert A., Bröckelmann P.J. The emerging role of immune checkpoint inhibition in malignant lymphoma. Haematologica, 2017, vol. 102, no. 1, pp. 30–42. doi: 10.3324/haematol.2016.150656
  10. Karbalaei M., Keikha M. Curcumin as an herbal inhibitor candidate against HTLV-1 protease. Jentashapir J. Health Res., 2019, vol. 10, no. 1: e92813. doi: 10.5812/jjhr.92813
  11. Karbalaei M., Keikha M. What is adult T-cell leukemia pathogenesis? System virology as a solution of this puzzle. Jundishapur. J. Chronic. Dis. Care, 2019, vol. 8, no. 3: e93351. doi: 10.5812/jjcdc.93351
  12. Keikha M., Eslami M., Yousefi B., Ali-Hassanzadeh M., Kamali A., Yousefi M., Karbalaei M. HCV genotypes and their determinative role in hepatitis C treatment. VirusDisease, 2020, vol. 31, no. 3, pp. 235–240. doi: 10.1007/s13337-020-00592-0
  13. Keikha M., Ghazvini K., Eslami M., Yousefi B., Casseb J., Yousefi M., Karbalaei M. Molecular targeting of PD-1 signaling pathway as a novel therapeutic approach in HTLV-1 infection. Microb. Pathog., 2020, vol. 144: 104198. doi: 10.1016/j.mic-path.2020.104198
  14. Keikha M., Karbalaei M. Overview on coinfection of HTLV-1 and tuberculosis: mini-review. J. Clin. Tuberc. Other Mycobact. Dis., 2021, vol. 23: 100224. doi: 10.1016/j.jctube.2021.100224
  15. Keikha M., Karbalaei Zadeh Babaki M., Marcondes Fonseca L.A., Casseb J. The relevance of HTLV-1-associated myelopathy/tropical spastic paraparesis in Iran: a review study. Rev. Clin. Med., 2019, vol. 6, no. 2, pp. 60–65. doi: 10.22038/RCM.2019.38759.1266
  16. Kinosada H., Yasunaga J.I., Shimura K., Miyazato P., Onishi C., Iyoda T., Inaba K., Matsuoka M. HTLV-1 bZIP factor enhances T-cell proliferation by impeding the suppressive signaling of co-inhibitory receptors. PLoS Pathog., 2017, vol. 13, no. 1: e1006120 . doi: 10.1371/journal.ppat.1006120
  17. Kinosada H., Yasunaga J.-I., Shimura K., Matsuoka M. Functional impairment of co-inhibitory receptors promotes T-cell proliferation in HTLV-1 associated adult T-cell leukemia cells. Blood, 2016, vol. 128, no. 22, p. 2516. doi: 10.1182/blood.V128.22.2516.2516
  18. Konnai S., Suzuki S., Shirai T., Ikebuchi R., Okagawa T., Sunden Y., Mingala C.N., Onuma M., Murata S., Ohashi K. Enhanced expression of LAG-3 on lymphocyte subpopulations from persistently lymphocytotic cattle infected with bovine leukemia virus. Comp. Immunol. Microbiol. Infect. Dis., 2013, vol. 36, no. 1, pp. 63–69. doi: 10.1016/j.cimid.2012.09.005
  19. Kozako T., Yoshimitsu M., Fujiwara H., Masamoto I., Horai S., White Y., Akimoto M., Suzuki S., Matsushita K., Uozumi K., Tei C., Arima N. PD-1/PD-L1 expression in human T-cell leukemia virus type 1 carriers and adult T-cell leukemia/lymphoma patients. Leukemia, 2009, vol. 23, no. 2, pp. 375–382. doi: 10.1038/leu.2008.272
  20. Lindsted T., Gad M., Grandal M.V., Frölich C., Bhatia V.K., Gjetting T., Lantto J., Horak I.D., Kragh M., Koefoed K., Pedersen M.W. Preclinical characterization of Sym023 a human anti-TIM3 antibody with a novel mechanism of action. AACR, 2018, vol. 78, no. 13: 5629. doi: 10.1158/1538-7445.AM2018-5629
  21. Lipson E.J., Long G.V., Tawbi H., Schadendorf D., Atkinson V.G., Maurer M., Simonsen K.L., Harbison C., Hodi F.S. CA224-047: a randomized, double-blind, phase II/III study of relatlimab (anti-LAG-3) in combination with nivolumab (anti-PD-1) versus nivolumab alone in previously untreated metastatic or unresectable melanoma. Ann. Oncol., 2018, vol. 29, no. 8, pp. viii464– viii465. doi: 10.1093/annonc/mdy289.058
  22. Menguy T., Briaux A., Jeunesse E., Giustiniani J., Calcei A., Guyon T., Mizrahi J., Haegel H., Duong V., Soler V., Brousset P., Bensussan A., Raymond Letron I., Le Bouteiller P. Anti-CD160, alone or in combination with bevacizumab, is a potent inhibitor of ocular neovascularization in rabbit and monkey. Invest. Ophthalmol. Vis. Sci., 2018, vol. 59, no. 7, pp. 2687–2698. doi: 10.1167/iovs.18-24024
  23. Mori N., Gill P.S., Mougdil T., Murakami S., Eto S., Prager D. Interleukin-10 gene expression in adult T-cell leukemia. Blood, 1996, vol. 88, no. 3, pp. 1035–1045.
  24. Mozhgani S.H., Zarei-Ghobadi M., Teymoori-Rad M., Mokhtari-Azad T., Mirzaie M., Sheikhi M., Jazayeri S.M., Shahbahrami R., Ghourchian H., Jafari M., Rezaee S.A., Norouzi M. Human T-lymphotropic virus 1 (HTLV-1) pathogenesis: a systems virology study. J. Cell Biochem., 2018, vol. 119, no. 5, pp. 3968–3979. doi: 10.1002/jcb.26546
  25. Ndhlovu L.C., Leal F.E., Hasenkrug A.M., Jha A.R., Carvalho K.I., Eccles-James I.G., Bruno F.R., Vieira R.G., York V.A., Chew G.M., Jones R.B., Tanaka Y., Neto W.K., Sanabani S.S., Ostrowski M.A., Segurado A.C., Nixon D.F., Kallas E.G. HTLV-1 tax specific CD8+ T cells express low levels of Tim-3 in HTLV-1 infection: implications for progression to neurological complications. PLoS Negl. Trop. Dis., 2011, vol. 5, no. 4: e1030. doi: 10.1371/journal.pntd.0001030
  26. Odorizzi P.M., Wherry E.J. Inhibitory receptors on lymphocytes: insights from infections. J. Immunol., 2012, vol. 188, no. 7, pp. 2957–2965. doi: 10.4049/jimmunol.1100038
  27. Ouaguia L., Mrizak D., Renaud S., Moralès O., Delhem N. Control of the inflammatory response mechanisms mediated by natural and induced regulatory T-cells in HCV-, HTLV-1-, and EBV-associated cancers. Mediators Inflamm., 2014: 564296. doi: 10.1155/2014/564296
  28. Rodríguez-Zúñiga M., Cortez-Franco F., Qujiano-Gomero E. Adult T-cell leukemia/lymphoma. Actas Dermosifiliogr. (Engl. Ed)., 2018, vol. 109, no. 5, pp. 399–407. doi: 10.1016/j.ad.2017.08.014
  29. Shimauchi T., Kabashima K., Nakashima D., Sugita K., Yamada Y., Hino R., Tokura Y. Augmented expression of programmed death-1 in both neoplastic and non-neoplastic CD4+ T-cells in adult T-cell leukemia/lymphoma. Int. J. Cancer, 2007, vol. 121, no. 12, pp. 2585–2590. doi: 10.1002/ijc.23042
  30. Virgin H.W., Wherry E.J., Ahmed R. Redefining chronic viral infection. Cell, 2009, vol. 138, no. 1, pp. 30–50. doi: 10.1016/j.cell.2009.06.036
  31. Workman C.J., Rice D.S., Dugger K.J., Kurschner C., Vignali D.A. Phenotypic analysis of the murine CD4 related glycoprotein, CD223 (LAG-3). Eur. J. Immunol., 2002, vol. 32, no. 8, pp. 2255–2263. doi: 10.1002/1521-4141(200208)32:8<2255::AID-IMMU2255>3.0.CO;2-A.
  32. Yasuma K., Yasunaga J.-I., Takemoto K., Sugata K., Mitobe Y., Takenouchi N., Nakagawa M., Suzuki Y., Matsuoka M. HTLV-1 bZIP factor impairs anti-viral immunity by inducing co-inhibitory molecule, T cell immunoglobulin and ITIM domain (TIGIT). PLoS Pathog., 2016, vol. 12, no. 1: e1005372. doi: 10.1371/journal.ppat.1005372
  33. Zarour H.M. Reversing T-cell dysfunction and exhaustion in cancer. Clin. Cancer Res., 2016, vol. 22, no. 8, pp. 1856–1864. doi: 10.1158/1078-0432.CCR-15-1849

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2021 Keikha M., Karbalaei M.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: серия ПИ № ФС 77 - 64788 от 02.02.2016.


This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies