The role of β-2-microglobulin in tumor development

Abstract

The tumor microenvironment (TME) is a dynamic ecosystem where cancer cells interact with the immune system to either promote or inhibit tumor progression.A crucial aspect of this interaction involves the major histocompatibility complex class I (MHC MHC-I) molecules on the surface of tumor cells. To analyze the role of this MHC MHC-I expression, we use the TC TC-1 mouse model of tumors induced by human papillomaviruses (HPVs). In our previous study, we identified functional differences between tumor tumor-associated macrophages in TC TC-1/A9 A9-induced tumors with reversibly reduced MHC MHC-I expression and TC TC-1/dB2m tumors with irreversible MHC MHC-I downregulation, which is mediated by knocking out the B2m gene encoding the light MHC MHC-I chain ββ-22-microglobulin (B2m) 1 . To extend our research, we developed a new TC TC-1/ dH2 cell line with deactivated H2H2-D and H2H2-K genes that code for the MHC MHC-I heavy chains.Comparing the TC TC-1/dB2m and TC TC-1/dH2 cell lines and tumors may reveal an intratumoral role of B2m that can function as a soluble growth factor in TME, and its deactivation can be responsible for the reduced proliferation of TC TC-1/dB2m cells and the decreased growth of TC TC-1/dB2m dB2m-induced tumors, compared to TC TC-1 cells and tumors, respectively 2 . However, we found that TC TC-1/dH2 cell proliferation was reduced similarly to that of TC TC-1/dB2m cells. Furthermore, TC TC-1/dH2 tumors resemble TC TC-1/dB2m tumors in terms of growth, resistance to immunotherapy against the HPV16 E7 oncoprotein, immune cell infiltration, and macrophage polarization. Therefore, we could not confirm that B2m deactivation contributes to changes in the properties of TC TC-1/dB2m cells and tumors by a mechanism other than MHC MHC-I downregulation. Single Single-cell RNA sequencing could uncover potential subtle differences in immune cells infiltrating TC TC-1/dB2m and TC TC-1/dH2 tumors.