Abstract P2-25-04: Granzyme B expression in tumor microenvironment as a biomarker for prognosis of triple-negative breast cancer

Abstract

Background: Many analyzes on tumor microenvironment has made it clear that tumor infiltrating lymphocytes (TILs) plays an important role in treating cancers with high tumor mutation burden such as triple-negative breast cancer (TNBC). We reported that the relationship between TILs and PD-L1 expression (Oncotarget 2017) and revealed that high-TILs/positive-PD-L1 expression population in TNBC was associated with better prognosis. However, its molecular mechanism is still unclear. Meanwhile, it was well-known that activated T-cells work as antitumor lymphocytes by enhancing the apoptosis by granzyme B (GZMB) and perforin, and then production of cytokines such as INFγ. We focused on GZMB and examined the function of activated T-cells. Patients and Methods: This study included 230 patients with primary TNBC who underwent resection without neoadjuvant chemotherapy at our three hospitals between January 2004 and December 2014. The immunohistochemistry (IHC) scoring for GZMB expression on TILs was defined as 1 or 5%. PD-L1 positivity was defined as ≥ 10 Combined Positive Score (CPS) based on tumor and immune cells staining positive for PD-L1. Results: Of the 230 TNBC, GZMB on TILs was expressed as more than 1% and 5% positive in 181 (79%) and 50 (22%) tumors, respectively, and PD-L1 and CD8 on TILs was expressed as positive in 99 (43%) and 127 (55%) tumors, respectively. GZMB expression (more than 5%) was significantly correlated with PD-L1 expression (P=0.0048) and CD8 expression (P=0.0156). 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 GZMB-positive tumors had a longer OS, compared to the patients with GZMB-negative tumors (P = 0.0155 in RFS and P = 0.0202 in OS) when PD-L1 expression on TILs was high, but not when it was low. Conclusion: OS was significantly longer among patients with high GZMB expressing TNBC. These results may validate the significance of GZMB as a biomarker for various immunotherapies in TNBC. Citation Format: Kimihisa Mizoguchi, Masafumi Nakamura. Granzyme B expression in tumor microenvironment as a biomarker for prognosis of triple-negative breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-25-04.