Abstract 1332: Major histocompatibility complex class I chain-related gene A and B expression induced by heavy ion beam irradiation in cervical cancer cells

Major histocompatibility complex class I chain-related gene A and B (MIC) are transmembrane glycoproteins to function as a ligand for human NKG2D that is a main activating receptor of NK cells. MIC is minimally expressed on normal cells, but frequently upregulated via viral infection, cellular stress signals, and malignant transformation. NKG2D recognizes MIC, resulting in the activation of NK cells. Recent progress on radiation biophysics has shown that photon or particle radiation can modulate anti-tumor immunity in host irradiated via regulation of immune recognition protein expression on cancer cells. The aim of this study is to investigate the effects of heavy ions beam irradiation on membrane MIC expression in human cervical cancer cells. We used HEK293 cells stably overexpressing HPV-E6 or E7 oncoproteins and 5 human cervical cancer cell lines in this study. Carbon ions beam irradiation (CIR, 290 MeV/n; LET, ∼70 keV/μm, mono peak), a beam of heavy ion beams, was performed at the in-house synchrotron accelerator that is able to produce carbon ion beams. Irradiated doses ranged from 0 to 10 Gy of carbon-ions. Cell membrane MIC expression was evaluated by flowcytometry using an anti-MIC antibody. MIC expression was upregulated in HPV-E6 or E7 overexpressing HEK293 cells and 5 human cervical cancer cells in a dose-dependent manner. HPV16-positive human cervical cancer Caski cells showed a remarkable upregulation of MIC expression after CIR. Other cervical cell lines (ME-180, HeLa, SiHa, and C33A) showed a modest MIC upregulation. E6- or E7-overexpressing HEK293 cells exhibited a considerable induction of MIC expression after CIR. We investigated the impact of DNA damage responses on HIR-mediated MIC upregulation using drug inhibitors of proteins that are involved in DNA damage responses. Both pharmacological Chk1 inhibition and ATM inhibition cancelled CIR-mediated MIC upregulation in HPV oncoprotein-positive HEK293 cells. The results indicated that ATM/ATR-Chk1 pathways were involved in MIC upregulation on HPV-positive cells including cervical cancer cells. These findings support the favorable combination of MIC-targeted therapy with heavy ion therapy against cervical cancers. Citation Format: Sumitaka Hasegawa, Nakako Nakajima. Major histocompatibility complex class I chain-related gene A and B expression induced by heavy ion beam irradiation in cervical cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1332.