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
Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Breast Center, Kumamoto Shinto General Hospital, 3-2-65 Oe, Chuo-ku, Kumamoto 862-8655, Japan.
Cancers (Basel). 2023 Sep 7;15(18):4456. 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.
肿瘤微环境中的肿瘤浸润淋巴细胞在三阴性乳腺癌（TNBC）的治疗中具有重要意义。细胞毒性T细胞会产生细胞因子和细胞毒性因子，如穿孔素和颗粒酶，它们通过损伤靶细胞来诱导细胞凋亡。为了识别这些细胞的生物标志物，我们对2004年1月至2014年12月期间230例未接受术前化疗而行手术的原发性TNBC患者的肿瘤微环境中的颗粒酶B（GZMB）进行了研究，将其作为治疗反应和预后的生物标志物。程序性细胞死亡配体1（PD-L1）阳性定义为基于肿瘤细胞和免疫细胞的PD-L1免疫染色的综合阳性评分≥10。GZMB高定义为肿瘤浸润淋巴细胞（TILs）中≥1%呈阳性。在230例TNBC患者中，117例（50.9%）有CD8阳性浸润性肿瘤。在PD-L1阳性组中，Kaplan-Meier分析显示，GZMB高的TNBC患者比GZMB低的患者具有更好的无复发生存期（RFS）和总生存期（OS），且OS显著更长（RFS： = 0.0220，OS： = 0.0254）。多变量分析还显示，PD-L1和GZMB高的患者OS显著更好（风险比：0.25（95%IC：0.07 - 0.88）， = 0.03）。我们的研究结果表明，GZMB是PD-L1阳性TNBC患者有用的预后生物标志物。
