Abstract 1272: Upregulation of mRNA of CD80, FOXP3, NKG2D and PD-L1 in peripheral blood mononuclear cells is associated with metastatic breast cancer patients

Abstract

Abstract BACKGROUND: Immune cells in the blood circulation may directly or indirectly interact with cancer cells including circulating tumor cells (CTCs), local and metastatic lesions during immune surveillance. Upon such interactions, the immune cells might be activated or inhibited in anti-rumor responses with several immune checkpoint pathways. However, little is known about alteration of immune checkpoint pathways in peripheral blood mononuclear cells (PBMCs) in the process of breast cancer progression. In the current study, we investigated the alteration of mRNA expression which is associated to immune checkpoint pathways in PBMCs of early and late stage breast cancer patients by comparing with healthy populations. PATIENTS AND METHODS: Twelve early operable breast cancer (EBC) patients, 30 metastatic breast cancer (MBC) patients in Kyoto University Hospital and 6 healthy volunteers (HV) participated. PBMCs were isolated by using cell preparation tubes according to the manufacturer's instruction. RNA was extracted from the total PBMCs and relative mRNA expressions of CD4, CD8, CD40, CD56, CD80. CTLA4, FOXP3, IDO1, IDO2, NKG2D, NRP1, PD-1, and PD-L1 were evaluated by quantitative RT-PCR. RESULT: The expressions of mRNA were not significantly changed between HV and EBC. By contrast, between HV or EBC and MBC, significant differences were detected in mRNA expression in CD80, FOXP3, NKG2D and PD-L1. All of them were upregulated in MBC, compared with HV or/and EBC (Reference Table 1). CONCLUSION: Based on the findings of the correlation between up-regulation of the immune check point molecules tested and metastatic cancer samples, it suggested that the development of breast cancer burden should be relevant to some specific immune resistance mechanism. Further careful evaluations of the current study will provide novel prospects for diagnostic biomarkers and therapeutic targets for management of breast cancer patients. Resultmean HV (ng/mL)mean EBC (ng/mL)mean MBC (ng/mL)EBC vs. HVEBC vs. HVMBC vs. HVMBC vs. HVMBC vs. EBCMBC vs. EBCp value95% CIp value95% CIp value95% CICD40.074460.90560.86520.2921-0.1404 to 0.43730.2728-0.08899 to 0.30520.6361-0.2114 to 0.1307CD81.2850.84181.1390.1896-1.129 to 0.24270.5976-0.7027 to 0.41070.0793-0.03641 to 0.6311CD400.70490.84941.0040.2892-0.1349 to 0.42390.0827-0.04087 to 0.63890.2334-0.1036 to 0.4127CD561.6372.4242.8750.4563-1.399 to 2.9740.2002-0.6881 to 3.1650.5711-1.144 to 2.046CD800.6761.4821.3250.0911-0.1445 yo 1.7560.0320.05925 to 1.2380.5747-0.7173 to 0.4036CTLA41.8273.0182.80.3655-1.519 to 3.9000.0918-0.1668 to 2.1120.746-1.567 to 1.131FOXP30.78011.0382.2960.4605-0.4647 to 0.98020.02780.1760 to 2.8570.01320.2776 to 2.240IDO11.0251.9841.4250.2317-0.6764 to 0.26120.3982-0.5508 to 1.3500.2437-1.516 to 0.3971IDO20.56780.35280.37990.3447-0.6912 to 0.26120.2673-0.5304 to 0.15450.8255-0.2222 to 0.2764NKG2D1.5421.1852.040.3976-1.228 to 0.51380.3432-0.5553 to 1.5520.03730.05292 to 1.658NRP11.8614.4371.1560.1359-0.9076 to 6.0580.3538-1.455 to 3.9470.2782-3.780 to 1.121PD-10.53520.35270.40090.1798-0.4582 to 0.093290.3895-0.4472 to 0.17870.6692-0.1783 to 0.2747PD-L10.87321.0372.2180.7193-0.7861 to 1.1140.03670.08793 to 2.6020.01730.2197 to 2.142 Citation Format: Ayane Yamaguchi, Kosuke Kawaguchi, Eiji Suzuki, Mariko Nishie, Masakazu Toi. Upregulation of mRNA of CD80, FOXP3, NKG2D and PD-L1 in peripheral blood mononuclear cells is associated with metastatic breast cancer patients. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1272. doi:10.1158/1538-7445.AM2015-1272