脂质滴相关 Perilipin-3：口腔鳞状细胞癌中的潜在免疫检查点和癌基因。
Lipid droplets-related Perilipin-3: potential immune checkpoint and oncogene in oral squamous cell carcinoma.
机构信息
Central Laboratory of Stomatology, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
Department of Oral and Maxillofacial Surgery, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
出版信息
Cancer Immunol Immunother. 2024 Mar 30;73(5):78. doi: 10.1007/s00262-024-03659-9.
BACKGROUND
Lipid droplets (LDs) as major lipid storage organelles are recently reported to be innate immune hubs. Perilipin-3 (PLIN3) is indispensable for the formation and accumulation of LDs. Since cancer patients show dysregulated lipid metabolism, we aimed to elaborate the role of LDs-related PLIN3 in oral squamous cell carcinoma (OSCC).
METHODS
PLIN3 expression patterns (n = 87), its immune-related landscape (n = 74) and association with B7-H2 (n = 51) were assessed by immunohistochemistry and flow cytometry. Real-time PCR, Western blot, Oil Red O assay, immunofluorescence, migration assay, spheroid-forming assay and flow cytometry were performed for function analysis.
RESULTS
Spotted LDs-like PLIN3 staining was dominantly enriched in tumor cells than other cell types. PLIN3 tumor showed high proliferation index with metastasis potential, accompanied with less CD3CD8 T cells in peripheral blood and in situ tissue, conferring immunosuppressive microenvironment and shorter postoperative survival. Consistently, PLIN3 knockdown in tumor cells not only reduced LD deposits and tumor migration, but benefited for CD8 T cells activation in co-culture system with decreased B7-H2. An OSCC subpopulation harbored PLIN3B7-H2 tumor showed more T cells exhaustion, rendering higher risk of cancer-related death (95% CI 1.285-6.851).
CONCLUSIONS
LDs marker PLIN3 may be a novel immunotherapeutic target in OSCC.
背景
脂滴（LDs）作为主要的脂质储存细胞器，最近被报道为先天免疫中心。脂滴包被蛋白 3（PLIN3）对于 LD 的形成和积累是必不可少的。由于癌症患者表现出脂质代谢失调，我们旨在阐述与 LD 相关的 PLIN3 在口腔鳞状细胞癌（OSCC）中的作用。
方法
通过免疫组织化学和流式细胞术评估 PLIN3 表达模式（n=87）、其免疫相关图谱（n=74）以及与 B7-H2 的关联（n=51）。实时 PCR、Western blot、油红 O 染色、免疫荧光、迁移实验、球体形成实验和流式细胞术用于功能分析。
结果
点状 LD 样 PLIN3 染色主要富集在肿瘤细胞中，而不是其他细胞类型。PLIN3 肿瘤表现出高增殖指数和转移潜能，同时外周血和原位组织中 CD3CD8 T 细胞较少，导致免疫抑制微环境和术后生存时间缩短。同样，肿瘤细胞中 PLIN3 的敲低不仅减少了 LD 沉积和肿瘤迁移，而且有利于与 B7-H2 共培养系统中 CD8 T 细胞的激活，降低了 B7-H2 的表达。OSCC 亚群中存在 PLIN3B7-H2 肿瘤的患者表现出更多的 T 细胞耗竭，使癌症相关死亡的风险更高（95%CI 1.285-6.851）。
结论
LD 标志物 PLIN3 可能是 OSCC 的一种新的免疫治疗靶点。
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