Abstract P4-06-22: Transcription factor T-bet and PD-L1 expression in tumor microenvironment of triple-negative breast cancer

Abstract

Abstract Background: Many analyzes regarding immunotherapies using checkpoint blockade has made it clear that tumor infiltrating lymphocytes (TILs) plays an important role in treating cancers with high levels of somatic mutations such as triple-negative breast cancer (TNBC). We reported the relationship between TILs and PD-L1 expression, and revealed that high-TILs/positive-PD-L1 expression population in TNBC was associated with better prognosis (Oncotarget 2017). However, its molecular mechanism is still unclear. Meanwhile, T-box transcription factor 21 (T-bet) which regulates effecter T-cells activation is derived by stimulation of T-cell receptor and IL-12. Activated T-cells work as antitumor lymphocytes by enhancing the production of cytokines such as INFγ. We focused on T-bet and examined the function of activated T-cells. Patients and Methods: This study included 242 patients with primary TNBC who underwent resection without neoadjuvant chemotherapy at our three hospitals between January 2004 and December 2014. The immunohistochemistry scoring for CD8 and T-bet expression on TILs was defined as ≥30 per 0.00625mm2. PD-L1 positivity was defined as ≥1% of tumor cells staining positive for PD-L1. Results: Of the 242 TNBC, CD8 on TILs was expressed as positive in 127 (52.5%) tumors, T-bet on TILs was expressed as positive in 67 (27.7%) tumors, and PD-L1 expression on tumor cells was expressed as positive in 99 (40.9%) tumors. T-bet expression was significantly correlated with CD8 expression (P<0.0001) and PD-L1 expression (P=0.0004). There was no significant difference in recurrence free survival (RFS) and overall survival (OS) regardless of CD8 or PD-L1expression level. Meanwhile, the patients with T-bet-positive tumors had a longer OS, compared to those with T-bet-negative tumors (P = 0.13 in RFS and P = 0.047 in OS). The multivariate analysis revealed that T-bet expression on TILswas an independent and positive prognostic factor for OS(HR = 0.5, 95%CI 0.1-0.9, P = 0.035). Conclusion: OS was significantly longer among patients with high T-bet expressing TNBC. These results may validate the significance of T-bet as a biomarker for various immunotherapies in TNBC. Citation Format: Mori H, Kubo M, Kai M, Kurata K, Kawaji H, Kaneshiro K, Motoyama Y, Kuroki R, Yamada M, Nishimura R, Okido M, Oda Y, Nakamura M. Transcription factor T-bet and PD-L1 expression in tumor microenvironment of triple-negative breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-06-22.