Kinoshita Fumihiko, Takada Kazuki, Wakasu Sho, Saito Shunichi, Hashinokuchi Asato, Matsudo Kyoto, Nagano Taichi, Akamine Takaki, Kohno Mikihiro, Takenaka Tomoyoshi, Shimokawa Mototsugu, Oda Yoshinao, Yoshizumi Tomoharu
Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Department of Surgery, Saiseikai Fukuoka General Hospital, Fukuoka, Japan.
Ann Surg Oncol. 2023 Nov;30(12):7579-7589. doi: 10.1245/s10434-023-14085-z. Epub 2023 Aug 16.
Granzyme B (GZMB) is a serine protease produced by cytotoxic lymphocytes that reflects the activity of anti-tumor immune responses in tumor-infiltrating lymphocytes (TILs); however, the prognostic significance of GZMB+ TILs in lung adenocarcinoma is poorly understood.
We analyzed 273 patients with pathological stage (pStage) I-IIIA lung adenocarcinoma who underwent surgery at Kyushu University from 2003 to 2012. We evaluated GZMB+ TIL counts by immunohistochemistry. We set the cut-off values at 12 cells/0.04 mm for GZMB+ TILs and divided the patients into GZMB-High (n = 171) and GZMB-Low (n = 102) groups. Then, we compared the clinicopathological characteristics of the two groups and clinical outcomes. Programmed cell death ligand-1 (PD-L1) and indoleamine 2,3-dioxygenase 1 (IDO1) expression in tumor cells was also evaluated, and combined prognostic analyses of GZMB+ TILs with PD-L1 or IDO1 were performed.
GZMB-Low was significantly associated with pStage II-III, PD-L1 positivity, and IDO1 positivity. Disease-free survival (DFS) and overall survival (OS) in the GZMB-Low group were significantly worse than in the GZMB-High group. In multivariable analysis, GZMB-Low was an independent prognostic factor for both DFS and OS. Furthermore, combined prognostic analyses of GZMB+ TILs with PD-L1 or IDO1 showed that GZMB-Low with high expression of these immunosuppressive proteins had the worst prognosis.
We analyzed GZMB+ TIL counts in lung adenocarcinoma and elucidated its prognostic significance and association with PD-L1 and IDO1. GZMB+ TIL counts might reflect the patient's immunity against cancer cells and could be a useful prognostic marker of lung adenocarcinoma.
颗粒酶B（GZMB）是一种由细胞毒性淋巴细胞产生的丝氨酸蛋白酶，反映肿瘤浸润淋巴细胞（TILs）中抗肿瘤免疫反应的活性；然而，GZMB+ TILs在肺腺癌中的预后意义尚不清楚。
我们分析了2003年至2012年在九州大学接受手术的273例病理分期（pStage）为I-IIIA期的肺腺癌患者。我们通过免疫组织化学评估GZMB+ TIL计数。我们将GZMB+ TILs的临界值设定为12个细胞/0.04平方毫米，并将患者分为GZMB高表达组（n = 171）和GZMB低表达组（n = 102）。然后，我们比较了两组的临床病理特征和临床结局。还评估了肿瘤细胞中程序性细胞死亡配体1（PD-L1）和吲哚胺2,3-双加氧酶1（IDO1）的表达，并对GZMB+ TILs与PD-L1或IDO1进行了联合预后分析。
GZMB低表达与pStage II-III期、PD-L1阳性和IDO1阳性显著相关。GZMB低表达组的无病生存期（DFS）和总生存期（OS）明显差于GZMB高表达组。在多变量分析中，GZMB低表达是DFS和OS的独立预后因素。此外，GZMB+ TILs与PD-L1或IDO1的联合预后分析表明，这些免疫抑制蛋白高表达的GZMB低表达患者预后最差。
我们分析了肺腺癌中GZMB+ TIL计数，阐明了其预后意义以及与PD-L1和IDO1的相关性。GZMB+ TIL计数可能反映患者对癌细胞的免疫力，可能成为肺腺癌有用的预后标志物。
