The role of platelets in premetastatic niche formation and metastasis (B05)

在第一个资助期，我们在非小细胞肺癌（NSCLC）中发现了肿瘤细胞/血小板串扰，这导致PD-L1从肿瘤细胞转移到血小板（pPD-L1）。由于pPD-L1被发现可以调节T细胞活性，并与肿瘤细胞上皮向间充质转化（EMT）的诱导有关，我们现在将通过实验探讨一种假设，即免疫调节蛋白从癌细胞向血小板的EMT依赖转移对于转移前生态位的形成至关重要。我们将进行详细的时间过程分析，以表征肿瘤发生和发展过程中肿瘤和血小板表面的蛋白质组学变化。最后，将启动一项前瞻性多中心生物标志物研究，以交叉验证和确认血小板表达生物标志物（包括先前确定的pPD-L1）在NSCLC患者中的作用。

In the first funding period, we identified a tumour cell/platelet crosstalk in non-small cell lung cancer (NSCLC), which leads to a transfer of PD-L1 from tumour cells to platelets (pPD-L1). As pPD-L1 was found to modulate T cell activity and is associated with induction of epithelial to mesenchymal transition (EMT) in tumour cells, we will now experimentally probe the hypothesis that an EMT dependent transfer of immunoregulatory proteins from cancer cells to platelets is crucial for the formation of the premetastatic niche. We will conduct a detailed time course analysis to characterise proteomic changes on the tumour and platelet surface during tumour initiation and progression. Finally, a prospective multicenter biomarker study will be initiated to cross-validate and confirm the role of platelet-expressed biomarkers (including previously identified pPD-L1) in NSCLC patients.