Granzyme B Expression in the Tumor Microenvironment as a Prognostic Biomarker for Patients with Triple-Negative Breast Cancer

• Published in: Cancers Vol. 15; no. 18; p. 4456
• Main Authors: Mizoguchi, Kimihisa, Kawaji, Hitomi, Kai, Masaya, Morisaki, Takafumi, Hayashi, Saori, Takao, Yuka, Yamada, Mai, Shimazaki, Akiko, Osako, Tomofumi, Arima, Nobuyuki, Okido, Masayuki, Oda, Yoshinao, Nakamura, Masafumi, Kubo, Makoto
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 07-09-2023; MDPI
• Subjects: Analysis; Antibodies; Apoptosis; Biomarkers; Breast cancer; Cancer; Cancer therapies; CD8 antigen; Cell death; Chemotherapy; Communication; Cytotoxic factors; Cytotoxicity; Gene amplification; Granzyme B; Health aspects; Immunohistochemistry; Immunotherapy; Lymphocytes; Lymphocytes T; Medical prognosis; Multivariate analysis; Patients; PD-L1 protein; Perforin; Prognosis; T cells; Tumor cells; Tumor microenvironment; Tumor-infiltrating lymphocytes; Tumors; Japan; United States > US; granzyme B; triple-negative breast cancer; immune checkpoint inhibitors; biomarker; programmed cell death ligand 1
• ISSN: 2072-6694; 2072-6694
• DOI: 10.3390/cancers15184456

Tumor-infiltrating lymphocytes in the tumor microenvironment are important in the treatment of triple-negative breast cancer (TNBC). Cytotoxic T cells produce cytokines and cytotoxic factors, such as perforin and granzyme, which induce apoptosis by damaging target cells. To identify biomarkers of these cells, we investigated granzyme B (GZMB) in the tumor microenvironment as a biomarker of treatment response and prognosis in 230 patients with primary TNBC who underwent surgery without preoperative chemotherapy between January 2004 and December 2014. Programmed cell death ligand 1 (PD-L1) positivity was defined as a composite positive score ≥10 based on the PD-L1 immunostaining of tumor cells and immune cells. GZMB-high was defined as positivity in ≥1% of tumor-infiltrating lymphocytes (TILs). Among the 230 TNBC patients, 117 (50.9%) had CD8-positive infiltrating tumors. In the PD-L1-positive group, a Kaplan-Meier analysis showed that GZMB-high TNBC patients had better recurrence-free survival (RFS) and overall survival (OS) than GZMB-low patients and that OS was significantly longer (RFS:
= 0.0220, OS:
= 0.0254). A multivariate analysis also showed significantly better OS in PD-L1- and GZMB-high patients (hazard ratio: 0.25 (95% IC: 0.07-0.88),
= 0.03). Our findings indicate that GZMB is a useful prognostic biomarker in PD-L1-positive TNBC patients.