Ntala Chara, Salji Mark, Salmond Jonathan, Officer Leah, Teodosio Ana Vieira, Blomme Arnaud, McGhee Ewan J, Powley Ian, Ahmad Imran, Kruithof-de Julio Marianna, Thalmann George, Roberts Ed, Goodyear Carl S, Jamaspishvili Tamara, Berman David M, Carlin Leo M, Le Quesne John, Leung Hing Y
CRUK Beatson Institute, Glasgow, UK.
Institute of Cancer Sciences, University of Glasgow, Garscube Estate, Switchback Road, Glasgow, UK.
Eur Urol Open Sci. 2021 May 25;29:19-29. doi: 10.1016/j.euros.2021.05.001. eCollection 2021 Jul.
Pelvic nodal metastasis in prostate cancer impacts patient outcome negatively.
To explore tumor-infiltrating immune cells as a potential predictive tool for regional lymph node (LN) metastasis.
We applied multiplex immunofluorescence and targeted transcriptomic analysis on 94 radical prostatectomy specimens in patients with (LN+) or without (LN-) pelvic nodal metastases. Both intraepithelial and stromal infiltrations of immune cells and differentially expressed genes (mRNA and protein levels) were correlated with the nodal status.
The identified CD4 effector cell signature of nodal metastasis was validated in a comparable independent patient cohort of 184 informative cases. Patient outcome analysis and decision curve analysis were performed with the CD4 effector cell density-based signature.
In the discovery cohort, both tumor epithelium and stroma from patients with nodal metastasis had significantly lower infiltration of multiple immune cell types, with stromal CD4 effector cells highlighted as the top candidate marker. Targeted gene expression analysis and confirmatory protein analysis revealed key alteration of extracellular matrix components in tumors with nodal metastasis. Of note, stromal CD4 immune cell density was a significant independent predictor of LN metastasis (odds ratio [OR] = 0.15, = 0.004), and was further validated as a significant predictor of nodal metastasis in the validation cohort (OR = 0.26, < 0.001).
Decreased T-cell infiltrates in the primary tumor (particularly CD4 effector cells) are associated with a higher risk of LN metastasis. Future evaluation of CD4-based assays on prostate cancer diagnostic biopsy materials may improve selection of at-risk patients for the treatment of LN metastasis.
In this report, we found that cancer showing evidence of cancer metastasis to the lymph nodes tends to have less immune cells present within the tumor. We conclude that the extent of immune cells present within a prostate tumor can help doctors determine the most appropriate treatment plan for individual patients.
前列腺癌盆腔淋巴结转移对患者预后有负面影响。
探讨肿瘤浸润免疫细胞作为区域淋巴结（LN）转移潜在预测工具的可能性。
设计、设置与参与者：我们对94例有（LN+）或无（LN-）盆腔淋巴结转移的前列腺癌根治术标本进行了多重免疫荧光和靶向转录组分析。免疫细胞的上皮内和基质浸润以及差异表达基因（mRNA和蛋白质水平）均与淋巴结状态相关。
在一个由184例信息完整病例组成的可比独立患者队列中验证了所确定的淋巴结转移CD4效应细胞特征。采用基于CD4效应细胞密度的特征进行患者预后分析和决策曲线分析。
在发现队列中，有淋巴结转移患者的肿瘤上皮和基质中多种免疫细胞类型的浸润均显著减少，其中基质CD4效应细胞被突出显示为首要候选标志物。靶向基因表达分析和验证性蛋白质分析揭示了有淋巴结转移肿瘤中细胞外基质成分的关键改变。值得注意的是，基质CD4免疫细胞密度是LN转移的显著独立预测因子（比值比[OR]=0.15，P=0.004），并在验证队列中进一步验证为淋巴结转移的显著预测因子（OR=0.26，P<0.001）。
原发肿瘤中T细胞浸润减少（尤其是CD4效应细胞）与LN转移风险较高相关。未来对前列腺癌诊断活检材料进行基于CD4的检测评估可能会改善LN转移高危患者的治疗选择。
在本报告中，我们发现显示有癌症转移至淋巴结证据的癌症往往肿瘤内存在的免疫细胞较少。我们得出结论，前列腺肿瘤内免疫细胞的程度可帮助医生为个体患者确定最合适的治疗方案。
