Department of Microbiology and Immunology, The University of Melbourne and The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.
Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark.
Front Immunol. 2021 Sep 2;12:668391. doi: 10.3389/fimmu.2021.668391. eCollection 2021.
The binding of platelet-derived growth factor D (PDGF-DD) to the NKp44 receptor activates a distinct transcriptional program in primary IL-2 expanded human natural killer (NK) cells. We were interested in knowing if the PDGF-DD-NKp44 pathway of NK cell activation might play a clinically relevant role in anti-tumor immunity. In order to address this question, we determined transcriptional signatures unique to resting, IL-2 expanded, and PDGF-DD activated, NK cells, in addition to different T cell subsets, and established the abundance of these immune cell phenotypes in The Cancer Genome Atlas (TCGA) low-grade glioma (LGG) dataset using CIBERSORT. Our results show that LGG patient tumors enriched for either the PDGF-DD activated NK cell or memory CD8 T cell phenotypes are associated with a more favorable prognosis. Combined cell phenotype analyses revealed that patients with LGG tumors enriched for the PDGF-DD activated NK cell phenotype and the CD4 T helper cell phenotype had a more favorable prognosis. High expression of transcripts encoding members of the killer cell lectin-like receptor (KLR) family, such as KLRK1 and KLRC2, KLRC3 and KLRC4 in LGG tumors were associated with more favorable prognosis, suggesting that these NK cell family receptors may play a prominent role in LGG anti-tumor immunity. Finally, many of the TCGA findings were reciprocated in LGG patients from the Chinese Glioma Genome Atlas (CGGA) dataset. Our results provide transcriptomic evidence that PDGF-DD activated NK cells and KLR family receptors may play an important clinical role in immune surveillance of LGG.
血小板衍生生长因子 D (PDGF-DD) 与 NKp44 受体的结合激活了原代 IL-2 扩增的人类自然杀伤 (NK) 细胞中的一个独特的转录程序。我们感兴趣的是，NK 细胞激活的 PDGF-DD-NKp44 途径是否可能在抗肿瘤免疫中发挥临床相关作用。为了回答这个问题，我们确定了静止、IL-2 扩增和 PDGF-DD 激活的 NK 细胞、不同 T 细胞亚群的独特转录特征，并使用 CIBERSORT 在癌症基因组图谱 (TCGA) 低级别神经胶质瘤 (LGG) 数据集确定这些免疫细胞表型的丰度。我们的结果表明，富含 PDGF-DD 激活的 NK 细胞或记忆 CD8 T 细胞表型的 LGG 患者肿瘤与更好的预后相关。联合细胞表型分析显示，富含 PDGF-DD 激活的 NK 细胞表型和 CD4 T 辅助细胞表型的 LGG 患者具有更好的预后。LGG 肿瘤中编码杀伤细胞凝集素样受体 (KLR) 家族成员的转录本，如 KLRK1 和 KLRC2、KLRC3 和 KLRC4 的高表达与更好的预后相关，这表明这些 NK 细胞家族受体可能在 LGG 抗肿瘤免疫中发挥重要作用。最后，TCGA 的许多发现在 CGGA 数据集的 LGG 患者中得到了回应。我们的结果提供了转录组学证据，表明 PDGF-DD 激活的 NK 细胞和 KLR 家族受体可能在 LGG 的免疫监测中发挥重要的临床作用。
