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.
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。