Meesters-Ensing Joyce I, Kranendonk Mariëtte E G, Hoogendijk Raoull, Hoving Eelco, Calkoen Friso G, van der Lugt Jasper, Carvalheiro Tiago, Nierkens Stefan
Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.
Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
Neurooncol Adv. 2025 May 17;7(1):vdaf097. doi: 10.1093/noajnl/vdaf097. eCollection 2025 Jan-Dec.
Current treatment options for pediatric high-grade brain tumors are limited, with poor 5-year overall survival rates. While immunotherapy is promising for these patients, the composition of their tumor immune microenvironment (TIME) is still not fully understood, due to the limited availability of tumor material for research. Given the high abundance of tumor tissue fragments obtained using the cavitron ultrasonic surgical aspirator (CUSA), these samples could serve as a resource for research and diagnostic purposes.
To evaluate CUSA tissue fragments as an alternative source for immune-landscape evaluation of brain tumors, we conducted immunological profiling on matched biopsy and CUSA-derived tissue fragments taken during resection from 11 pediatric brain tumor patients, using spectral flow cytometry and functional assays.
Cellular compositions were largely comparable between the two sources, both in freshly isolated and cryopreserved samples. Minor differences observed between biopsy and CUSA-derived tissue fragments from individual samples, likely reflect differences related with distinct tumor locations, caused by the small numbers of cells analyzed from one single biopsy versus multiple tumor sites collected with CUSA. Notably, expression of specific cellular immune subsets and their receptors indicating activation or regulation, were highly comparable between both materials, illustrating that CUSA can be used for detailed analyses of a multitude of immune cells and their functional markers. Moreover, CD8 + T-cells are enriched in tumor-infiltrating lymphocyte populations, maintaining their cytotoxic and proliferative capacity upon TCR (co)stimulation.
Our findings demonstrate that CUSA-derived tissue fragments represent the TIME in pediatric brain tumors, offering a valuable sample resource for further research.
小儿高级别脑肿瘤目前的治疗选择有限，5年总生存率较低。虽然免疫疗法对这些患者很有前景，但由于用于研究的肿瘤材料有限，其肿瘤免疫微环境（TIME）的组成仍未完全了解。鉴于使用超声外科吸引器（CUSA）获得的肿瘤组织碎片数量丰富，这些样本可作为研究和诊断的资源。
为了评估CUSA组织碎片作为脑肿瘤免疫图谱评估的替代来源，我们使用光谱流式细胞术和功能测定法，对11例小儿脑肿瘤患者切除术中获取的匹配活检组织和CUSA衍生组织碎片进行了免疫分析。
在新鲜分离和冷冻保存的样本中，两种来源的细胞组成在很大程度上具有可比性。个别样本的活检组织和CUSA衍生组织碎片之间观察到的微小差异，可能反映了与不同肿瘤位置相关的差异，这是由于单次活检分析的细胞数量较少，而CUSA收集了多个肿瘤部位。值得注意的是，两种材料之间特定细胞免疫亚群及其表明激活或调节的受体的表达高度可比，这说明CUSA可用于详细分析多种免疫细胞及其功能标志物。此外，CD8 + T细胞在肿瘤浸润淋巴细胞群体中富集，在TCR（共）刺激后保持其细胞毒性和增殖能力。
我们的研究结果表明，CUSA衍生的组织碎片代表了小儿脑肿瘤中的TIME，为进一步研究提供了有价值的样本资源。
