Influence of Treg-cell subpopulations on HLA-E expression by chronic myeloid leukemia and Burkitt's B-cell lymphoma cells
Main Article Content
Authors
S.A. Kan
M.A. Aitkhozhin’s Institute of Molecular Biology and Biochemistry, Dosmukhamedov str. 86, 050012, tel. +7(727) 2937092, Almaty, Kazakhstan
Almaty Branch of the National Center for Biotechnology, 14 Zhahanger St., Almaty, 050054, Kazakhstan
Al-Farabi Kazakh National University, Almaty, the Republic of Kazakhstan
A.V. Lushova
M.A. Aitkhozhin’s Institute of Molecular Biology and Biochemistry, Dosmukhamedov str. 86, 050012, tel. +7(727) 2937092, Almaty, Kazakhstan
Almaty Branch of the National Center for Biotechnology, 14 Zhahanger St., Almaty, 050054, Kazakhstan
Al-Farabi Kazakh National University, Almaty, the Republic of Kazakhstan
Ye.O. Ostapchuk
M.A. Aitkhozhin’s Institute of Molecular Biology and Biochemistry, Dosmukhamedov str. 86, 050012, tel. +7(727) 2937092, Almaty, Kazakhstan
Almaty Branch of the National Center for Biotechnology, 14 Zhahanger St., Almaty, 050054, Kazakhstan
ECO-Consulting LLC, 143/93 Abay St., 4b Off., Almaty, 040907, Kazakhstan
Abstract
Modern research in the field of cancer immunology traditionally identifies T regulatory (Treg) cells as key suppressors of the antitumor immune response due to their direct inhibitory effects on effector populations, such as natural killer (NK) cells and cytotoxic T lymphocytes. However, the direct influence of Treg cells on the biological and immunosuppressive properties of the tumor cells themselves remains insufficiently understood. Hematologic malignancies, including chronic myeloid leukemia and Burkitt’s lymphoma, are hematopoietic neoplasms associated with a highly unfavorable prognosis during progression, largely driven by the tumor's ability to establish an immune-privileged microenvironment. In this study, we investigated the effect of natural (nTreg) and induced (iTreg) regulatory T cells on the expression of immunosuppressive molecules by chronic myeloid leukemia (K562) and Burkitt's B-cell lymphoma (Raji) cell lines in vitro. K562 and Raji cells were cultured either in direct contact with Treg cell subpopulations or in their culture supernatants, followed by flow cytometric analysis of immunosuppressive marker expression. We demonstrated that direct cell-to-cell contact with both nTreg and iTreg cells leads to a statistically significant upregulation of HLA-E expression on the surface of both investigated cell lines. These findings indicate that regulatory T cells are capable of modifying the tumor immunophenotype, thereby enhancing the capacity for immune evasion. Consequently, the results of this study expand current understanding of the role of Treg cells in the progression of hematologic malignancies and emphasize the necessity of considering their direct impact on tumor cells when developing novel immunotherapeutic strategies.
Keywords
T regulatory cells, chronic myeloid leukemia, Burkitt's B-cell lymphoma, HLA-E, markers of immunosuppression
Article Details
References
Kim J.H., Kim B.S., Lee S.K. Regulatory T cells in tumor microenvironment and approach for anticancer immunotherapy // Immune Netw. – 2020. – Vol. 20, № 1. – P. e4.
Adeegbe D.O., Nishikawa H. Natural and induced T regulatory cells in cancer // Front. Immunol. – 2013. – Vol. 4. – P. 190.
Chatenoud L. Natural and Induced T CD4+CD25+FOXP3+ Regulatory T Cells // Methods Mol. Biol. – 2011. – Vol. 677. – P. 3-13.
Wang Y., Li J., Nakahata S., Iha H. Complex Role of Regulatory T Cells (Tregs) in the Tumor Microenvironment: Their Molecular Mechanisms and Bidirectional Effects on Cancer Progression // Int. J. Mol. Sci. – 2024. – Vol. 25, № 13. – P. 7346. Crossref
Facciabene A., Motz G.T., Coukos G. T Regulatory Cells: Key Players in Tumor Immune Escape and Angiogenesis // Cancer Res. – 2012. – Vol. 72, № 9. – P. 2162-2171.
Guo Q., Zhou Y., Xie T., Yuan Y., Li H., Shi W., Zheng L., Li X., Zhang W. Tumor microenvironment of cancer stem cells: Perspectives on cancer stem cell targeting // Genes Dis. – 2024. – Vol. 11, № 3. – P. 101043. doi: 10.1016/j.gendis.2023.05.024
Diefenbach A., Raulet D.H. Strategies for target cell recognition by natural killer cells // Immunol. Rev. – 2001. – Vol. 181. – P. 170-184. doi: 10.1034/j.1600-065x.2001.1810114.x
Lo Monaco E., Tremante E., Cerboni C., Melucci E., Sibilio L., Zingoni A., Nicotra M.R., Natali P.G., Giacomini P. Human leukocyte antigen E contributes to protect tumor cells from lysis by natural killer cells // Neoplasia. – 2011. – Vol. 13, № 9. – P. 822-830. doi: 10.1593/neo.101684
Sanchez-Correa B., Valhondo I., Hassouneh F., et al. DNAM-1 and the TIGIT/PVRIG/TACTILE Axis: Novel Immune Checkpoints for Natural Killer Cell-Based Cancer Immunotherapy // Cancers (Basel). – 2019. – Vol. 11, № 6. – P. 877. doi: 10.3390/cancers11060877
Hsu P., Santner-Nanan B., Hu M., Skarratt K., Lee C.H., Stormon M., Wong M., Fuller S.J., Nanan R. IL-10 Potentiates Differentiation of Human Induced Regulatory T Cells via STAT3 and Foxo1 // J. Immunol. – 2015. – Vol. 195, № 8. – P. 3665-3674. doi: 10.4049/jimmunol.1402898
Togashi Y., Shitara K., Nishikawa H. Regulatory T cells in cancer immunosuppression — implications for anticancer therapy // Nat. Rev. Clin. Oncol. – 2019. – Vol. 16, № 6. – P. 356-371.
Niedźwiecki M., Budziło O., Zieliński M., et al. CD4+CD25highCD127low/-FoxP3+ Regulatory T Cell Subpopulations in the Bone Marrow and Peripheral Blood of Children with ALL: Brief Report // J. Immunol. Res. – 2018. – Vol. 2018. – P. 1292404. doi: 10.1155/2018/1292404
D'Arena G., Vitale C., Coscia M., et al. Regulatory T Cells and Their Prognostic Relevance in Hematologic Malignancies // J. Immunol. Res. – 2017. – Vol. 2017. – P. 1832968. doi: 10.1155/2017/1832968
Kochan G., Escors D., Breckpot K., Guerrero-Setas D. Role of non-classical MHC class I molecules in cancer immunosuppression // Oncoimmunology. – 2013. – Vol. 2, № 11. – P. e26491. doi: 10.4161/onci.26491
Kamiya T., Seow S.V., Wong D., et al. Blocking expression of the inhibitory receptor NKG2A overcomes tolerance of NK cells // J. Clin. Invest. – 2019. – Vol. 129, № 5. – P. 2094-2106. Crossref
Fisher J.G., Doyle A.D.P., Graham L.V., et al. Disruption of the NKG2A:HLA-E immune checkpoint axis to enhance NK cell activation against cancer // Vaccines (Basel). – 2022. – Vol. 10, № 12. – P. 1993.
Matthew D.B., Salim I.K. Harnessing natural killer cell effector function against cancer // Immunother. Adv. – 2024. – Vol. 4, № 1. – P. ltad031. Crossref
Caocci G., Greco M., Fanni D., Senes G., Littera R., Lai S., et al. HLA-G expression and role in advanced-stage classical Hodgkin lymphoma // Eur. J. Histochem. – 2016. – Vol. 60, № 2. – P. 2606. URL
Reimers M.S., Engels C.C., Putter H., et al. Prognostic value of HLA class I, HLA-E, HLA-G and Tregs in rectal cancer: a retrospective cohort study // BMC Cancer. – 2014. – Vol. 14. – P. 486. Crossref
Chen D., Gu X., Liu J., et al. Notch signaling in the tumor microenvironment: recent advances and targeted therapeutics // Mol. Cancer. – 2024. – Vol. 25. – P. 50. Crossref
Arai J., Otoyama Y., Nozawa H., et al. The immunological role of ADAMs in the field of gastroenterological chronic inflammatory diseases and cancers: a review // Oncogene. – 2023. – Vol. 42, № 8. – P. 549-558.