Department of Gastroenterological Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan.
Department of Molecular Pathology, Osaka City University Graduate School of Medicine, Osaka, Japan.
Cancer Sci. 2021 May;112(5):1746-1757. doi: 10.1111/cas.14888. Epub 2021 Apr 1.
Several studies have reported that tissue-resident memory T cells (TRM cells) or tertiary lymphoid structures (TLSs) are associated with a good prognosis. The aim of this study was to clarify the association of TRM cells and TLSs in the tumor immune microenvironment in gastric cancer (GC). We performed immunohistochemical and immunofluorescence staining to detect the presence of CD103 T cells and to assess the association between CD103 T cells and TLSs. CD103 T cells were observed in the tumor epithelium accompanied by CD8 T cells and were associated with a better prognosis in GC. Furthermore, CD103 T cells were located around TLSs, and patients with CD103 had more rich TLSs. Patients who had both CD103 cells and who were TLS-rich had a better prognosis than patients with CD103 cells and who were TLS-poor. Moreover, for patients who received PD-1 blockade therapy, CD103 and TLS-rich predicted a good response. Flow cytometry was performed to confirm the characteristics of CD103 CD8 T cells and showed that CD103 CD8 T cells in GC expressed higher levels of PD-1, granzyme B, and interferon-γ than CD103 CD8 T cells. Our results suggested that CD103 CD8 cells in GC are correlated with TLSs, resulting in enhanced antitumor immunity in GC.
多项研究表明,组织驻留记忆 T 细胞(TRM 细胞)或三级淋巴结构(TLS)与良好的预后相关。本研究旨在阐明胃癌(GC)肿瘤免疫微环境中 TRM 细胞与 TLS 的相关性。我们进行了免疫组织化学和免疫荧光染色,以检测 CD103 T 细胞的存在,并评估 CD103 T 细胞与 TLS 之间的关联。在肿瘤上皮中观察到 CD103 T 细胞,伴随 CD8 T 细胞,与 GC 的良好预后相关。此外,CD103 T 细胞位于 TLS 周围,且 CD103 阳性患者具有更丰富的 TLS。同时具有 CD103 细胞和丰富 TLS 的患者比具有 CD103 细胞和缺乏 TLS 的患者预后更好。此外,对于接受 PD-1 阻断治疗的患者,CD103 和 TLS 丰富预测反应良好。通过流式细胞术证实了 CD103 CD8 T 细胞的特征,并表明 GC 中的 CD103 CD8 T 细胞表达更高水平的 PD-1、颗粒酶 B 和干扰素-γ,高于 CD103 CD8 T 细胞。我们的结果表明,GC 中的 CD103 CD8 细胞与 TLS 相关,导致 GC 中增强的抗肿瘤免疫。