PDF(Pubmed)
Abstract：
BACKGROUND: Tumor cell-induced platelet aggregation (TCIPA) is not only a recognized mechanism for paraneoplastic thrombocytosis but also a potential breakthrough alternative for a low response to immune checkpoint inhibitors (ICIs) in hematogenous metastasis of malignant melanoma (MM). However, there is no TCIPA-specific model for further investigation of the relationship among TCIPA, the tumor immune microenvironment (TIME), and metastasis.
METHODS: We developed a TCIPA metastatic melanoma model with advanced hematogenous metastasis and enhanced TCIPA characteristics. We also investigated the pathway for TCIPA in the TIME.
RESULTS: We found that TCIPA triggers the recruitment of tumor-associated macrophages (TAMs) to lung metastases by secreting B16 cell-educated platelet-derived chemokines such as CCL2, SDF-1, and IL-1β. Larger quantities of TAMs in the TCIPA model were polarized to the M2 type by B16 cell reprocessing, and their surface programmed cell death 1 ligand 1 (PD-L1) expression was upregulated, ultimately assisting B16 cells in escaping host immunity and accelerating MM hematogenous metastasis.
CONCLUSIONS: TCIPA accelerates MM lung metastasis via tumor-educated platelets (TEPs), triggering TAM recruitment, promoting TAM polarization (M2), and remodeling the suppressive TIME in lung metastases.
METHODS: We developed a TCIPA metastatic melanoma model with advanced hematogenous metastasis and enhanced TCIPA characteristics. We also investigated the pathway for TCIPA in the TIME.
RESULTS: We found that TCIPA triggers the recruitment of tumor-associated macrophages (TAMs) to lung metastases by secreting B16 cell-educated platelet-derived chemokines such as CCL2, SDF-1, and IL-1β. Larger quantities of TAMs in the TCIPA model were polarized to the M2 type by B16 cell reprocessing, and their surface programmed cell death 1 ligand 1 (PD-L1) expression was upregulated, ultimately assisting B16 cells in escaping host immunity and accelerating MM hematogenous metastasis.
CONCLUSIONS: TCIPA accelerates MM lung metastasis via tumor-educated platelets (TEPs), triggering TAM recruitment, promoting TAM polarization (M2), and remodeling the suppressive TIME in lung metastases.
摘要：
背景：肿瘤细胞诱导的血小板聚集（TCIPA）不仅是公认的副肿瘤性血小板增多的机制，而且是恶性黑色素瘤（MM）血行转移中对免疫检查点抑制剂（ICIs）低反应的潜在突破性替代方法。然而,没有TCIPA特定的模型来进一步研究TCIPA之间的关系，肿瘤免疫微环境（TIME），和转移。
方法：我们开发了一种具有晚期血行转移和增强TCIPA特征的TCIPA转移性黑色素瘤模型。我们还研究了TCIPA在TIME中的通路。
结果：我们发现TCIPA通过分泌B16细胞诱导的血小板源性趋化因子如CCL2、SDF-1和IL-1β，触发肿瘤相关巨噬细胞（TAM）募集到肺转移。通过B16细胞后处理，TCIPA模型中大量的TAM极化为M2型，它们的表面程序性细胞死亡1配体1(PD-L1)表达上调，最终帮助B16细胞逃避宿主免疫并加速MM血行转移。
结论：TCIPA通过肿瘤培养的血小板（TEPs）加速MM肺转移，触发TAM招募，促进TAM极化（M2），重塑肺转移的抑制时间。
方法：我们开发了一种具有晚期血行转移和增强TCIPA特征的TCIPA转移性黑色素瘤模型。我们还研究了TCIPA在TIME中的通路。
结果：我们发现TCIPA通过分泌B16细胞诱导的血小板源性趋化因子如CCL2、SDF-1和IL-1β，触发肿瘤相关巨噬细胞（TAM）募集到肺转移。通过B16细胞后处理，TCIPA模型中大量的TAM极化为M2型，它们的表面程序性细胞死亡1配体1(PD-L1)表达上调，最终帮助B16细胞逃避宿主免疫并加速MM血行转移。
结论：TCIPA通过肿瘤培养的血小板（TEPs）加速MM肺转移，触发TAM招募，促进TAM极化（M2），重塑肺转移的抑制时间。
