CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Increased tumor-infiltrating plasmacytoid dendritic cells express high levels of PD-L2 and affect CD8(+) T lymphocyte infiltration in human laryngeal squamous cell carcinoma.
Increased tumor-infiltrating plasmacytoid dendritic cells express high levels of PD-L2 and affect CD8(+) T lymphocyte infiltration in human laryngeal squamous cell carcinoma.
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肿瘤浸润浆细胞样树突状细胞(TI-pDC)在多种人类实体瘤中的浸润模式和预后意义已得到阐明,但其在喉鳞状细胞癌(LSCC)中的浸润模式和功能意义尚不清楚。
本研究采用流式细胞术分析 LSCC 患者肿瘤组织(TT)、癌旁组织(PT)和外周血(PB)中树突状细胞、T 淋巴细胞及其亚群的浸润情况。对连续组织切片进行 CD4、CD8 免疫组化和 CD123 免疫荧光染色,以研究 TI-pDC 与肿瘤浸润 T 淋巴细胞(TIL)在肿瘤微环境(TME)中的共定位。
结果显示,PB 中三种 DC 亚群比例均显著低于 TT 和 PT。值得注意的是,TT 中 pDC 比例明显高于 PT。与 N0 期患者相比,N+ 期患者 TI-pDC 比例显著升高。生存分析一致显示,TI-pDC 高浸润提示预后不良。
进一步分析发现 TI-pDC 与 CD8+ TIL 呈显著负相关;值得注意的是,PT 中 pDC 表达抑制性表面分子 PD-L2,而非 PD-L1。
总体而言,TI-pDC 增多与 LSCC 患者不良结局相关,且呈现抑制性表型,可能在 LSCC 肿瘤中抑制 CD8+ TIL。结果提示,靶向 PD-L2+ pDC 或可成为 LSCC 免疫治疗策略。
The infiltration and prognostic significance of tumor-infiltrating plasmacytoid dendritic cells (TI-pDC) have been elucidated in various human solid cancers.
However, the infiltrating patterns and functional importance of TI-pDC in laryngeal squamous cell carcinoma (LSCC) remain unknown. In this study, flow cytometric analyses were conducted to characterize the infiltration of dendritic cells and T lymphocytes, along with their respective subgroups in tumor tissues (TT), para-carcinoma tissues (PT), and peripheral blood (PB) from LSCC patients.
Immunohistochemical staining for CD4 and CD8, as well as immunofluorescence staining for CD123, were performed on serial tissue sections to investigate the co-localization of TI-pDC and tumor-infiltrating T lymphocytes (TIL) within the tumor microenvironment (TME).
Our results demonstrated significantly lower percentages of all three DC subsets in PB compared to TT and PT.
Notably, the pDC percentage was markedly higher in TT than in PT.
Moreover, TI-pDC percentage was significantly elevated in N + stage patients compared to those with N0 stage. The results of survival analysis consistently demonstrated that high levels of TI-pDC infiltration were indicative of a poor prognosis.
Further investigation revealed a significant negative correlation between TI-pDC and CD8 + TILs; notably, pDCs expressed an inhibitory surface molecule PD-L2 rather than PD-L1 within PT. Collectively, our findings suggest that increased TI-pDC is associated with adverse outcomes in LSCC patients while exhibiting an inhibitory phenotype that may play a crucial role in suppressing CD8 + TILs within LSCC tumors. These results highlight the potential therapeutic strategy targeting PD-L2 + pDCs for immunotherapies against LSCC.
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