Bassoy Esen Yonca, Chiusolo Valentina, Jacquemin Guillaume, Riccadonna Cristina, Walker Paul R, Martinvalet Denis
Department of Cell Physiology and Metabolism University of Geneva, 1211, Geneva, Switzerland.
Geneva University Hospitals and University of Geneva, Centre of Oncology, 1211, Geneva, Switzerland.
PLoS One. 2016 Apr 13;11(4):e0153433. doi: 10.1371/journal.pone.0153433. eCollection 2016.
Glioblastoma multiforme, the most aggressive primary brain tumor, is maintained by a subpopulation of glioma cells with self-renewal properties that are able to recapitulate the entire tumor even after surgical resection or chemo-radiotherapy. This typifies the vast heterogeneity of this tumor with the two extremes represented on one end by the glioma stemlike cells (GSC) and on the other by the glioma differentiated cells (GDC). Interestingly, GSC are more sensitive to immune effector cells than the GDC counterpart. However, how GSC impact on the killing on the GDC and vice versa is not clear. Using a newly developed cytotoxicity assay allowing to simultaneously monitor cytotoxic lymphocytes-mediated killing of GSC and GDC, we found that although GSC were always better killed and that their presence enhanced the killing of GDC. In contrast, an excess of GDC had a mild protective effect on the killing of GSC, depending on the CTL type. Overall, our results suggest that during combination therapy, immunotherapy would be the most effective after prior treatment with conventional therapies.
多形性胶质母细胞瘤是最具侵袭性的原发性脑肿瘤，由具有自我更新特性的胶质瘤细胞亚群维持，即使在手术切除或放化疗后，这些细胞仍能重现整个肿瘤。这体现了该肿瘤的巨大异质性，其两个极端，一端是胶质瘤干细胞（GSC），另一端是胶质瘤分化细胞（GDC）。有趣的是，GSC比其对应的GDC对免疫效应细胞更敏感。然而，GSC如何影响对GDC的杀伤，反之亦然，目前尚不清楚。使用一种新开发的细胞毒性检测方法，能够同时监测细胞毒性淋巴细胞介导的对GSC和GDC的杀伤作用，我们发现尽管GSC总是更容易被杀伤，并且它们的存在增强了对GDC的杀伤。相反，过量的GDC对GSC的杀伤有轻微的保护作用，这取决于CTL的类型。总体而言，我们的结果表明，在联合治疗期间，免疫疗法在先接受传统疗法治疗后将是最有效的。
