Institute of Oral Biology, College of Dentistry, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan.
Department of Dentistry, College of Dentistry, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan.
Int J Mol Sci. 2023 Mar 21;24(6):5931. doi: 10.3390/ijms24065931.
Immune modulation is a critical factor in determining the survival of patients with malignancies, including those with oral squamous cell carcinoma (OSCC) and head and neck SCC (HNSCC). Immune escape or stimulation may be driven by the B7/CD28 family and other checkpoint molecules, forming ligand-receptor complexes with immune cells in the tumor microenvironment. Since the members of B7/CD28 can functionally compensate for or counteract each other, the concomitant disruption of multiple members of B7/CD28 in OSCC or HNSCC pathogenesis remains elusive. Transcriptome analysis was performed on 54 OSCC tumors and 28 paired normal oral tissue samples. Upregulation of CD80, CD86, PD-L1, PD-L2, CD276, VTCN1, and CTLA4 and downregulation of L-ICOS in OSCC relative to the control were noted. Concordance in the expression of CD80, CD86, PD-L1, PD-L2, and L-ICOS with CD28 members was observed across tumors. Lower ICOS expression indicated a worse prognosis in late-stage tumors. Moreover, tumors harboring higher PD-L1/ICOS, PD-L2/ICOS, or CD276/ICOS expression ratios had a worse prognosis. The survival of node-positive patients was further worsened in tumors exhibiting higher ratios between PD-L1, PD-L2, or CD276 and ICOS. Alterations in T cell, macrophage, myeloid dendritic cell, and mast cell populations in tumors relative to controls were found. Decreased memory B cells, CD8 T cells, and Tregs, together with increased resting NK cells and M0 macrophages, occurred in tumors with a worse prognosis. This study confirmed frequent upregulation and eminent co-disruption of B7/CD28 members in OSCC tumors. The ratio between PD-L2 and ICOS is a promising survival predictor in node-positive HNSCC patients.
免疫调节是决定恶性肿瘤患者，包括口腔鳞状细胞癌（OSCC）和头颈部 SCC（HNSCC）患者生存的关键因素。免疫逃逸或刺激可能是由 B7/CD28 家族和其他检查点分子驱动的，它们与肿瘤微环境中的免疫细胞形成配体-受体复合物。由于 B7/CD28 的成员可以在功能上相互补偿或拮抗，因此在 OSCC 或 HNSCC 发病机制中同时破坏多个 B7/CD28 成员仍然难以捉摸。对 54 例 OSCC 肿瘤和 28 对配对正常口腔组织样本进行了转录组分析。与对照相比，OSCC 中 CD80、CD86、PD-L1、PD-L2、CD276、VTCN1 和 CTLA4 的上调和 L-ICOS 的下调。在肿瘤中观察到 CD80、CD86、PD-L1、PD-L2 和 L-ICOS 与 CD28 成员表达的一致性。ICOS 表达较低表明晚期肿瘤预后较差。此外，PD-L1/ICOS、PD-L2/ICOS 或 CD276/ICOS 表达比值较高的肿瘤预后较差。PD-L1、PD-L2 或 CD276 与 ICOS 比值较高的肿瘤中，阳性淋巴结患者的生存进一步恶化。与对照相比，在肿瘤中发现 T 细胞、巨噬细胞、髓样树突状细胞和肥大细胞群体发生改变。在预后较差的肿瘤中，记忆 B 细胞、CD8 T 细胞和 Tregs 减少，而静止 NK 细胞和 M0 巨噬细胞增加。本研究证实了 B7/CD28 成员在 OSCC 肿瘤中频繁上调和显著共破坏。PD-L2 和 ICOS 之间的比值是阳性淋巴结 HNSCC 患者有前途的生存预测指标。
Zotero 插件
