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Establishment and characterization of mouse tumor cell line with irreversible downregulation of MHC class I molecules
Lhotáková, Karolína ; Poláková, Ingrid (advisor) ; Černý, Jan (referee)
Malignant diseases are one of the major causes of death worldwide and the most common reason is the ability of tumor cells to escape the immune system. One of the main mechanisms used by tumors to avoid the immune response is downregulation of MHCI expression. In this thesis, the preparation of tumor cell line with irreversible downregulation of B2m is described. Inactivation of B2m was confirmed by flow cytometry. However, MHCI heavy chain H2-Db were expressed at the cell surface in a small amount after stimulation with IFNγ. In vitro proliferation of this clone was decreased. The tumor formation was delayed, and this effect was mediated by NK cells that played the major role in antitumor immunity. Metastatic activity of these cells was not affected after inactivation of B2m. TC-1/dB2m cells are not sensitive to DNA immunization. In combined immunotherapy experiments with DNA vaccinaton and ODN1826 adjuvant, a weak deceleration of tumor growth was achieved repeatedly. TC-1/dB2m induced tumors contained more CD4+ T lymphocytes, Treg, γδ T lymfocytes and plasmacytoid dendritic cells, and fewer NK cells and macrophages than tumors induced by original TC-1 cells. Moreover, combined immunotherapy did not increase the infiltration of the TC-1/dB2m tumors with immune cells. The TC-1/dB2m tumor cell line...
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