血小板来源PD-L1在肿瘤血行转移中的免疫抑制效应及其靶向治疗策略

doi:10.3969/j.issn.1006-5725.2026.15.007

Abstract

Abstract:

Platelets are the second most abundant cellular component in blood after erythrocytes and have traditionally been recognized primarily for their roles in hemostasis and thrombosis. The expression of programmed death-ligand 1 （PD-L1） on the platelet surface enables direct inhibition of T cell function. Moreover， platelets can form a physical barrier by surrounding circulating tumor cells （CTCs）， thereby amplifying immunosuppressive signals synergistically and establishing a mobile immune barrier during hematogenous tumor metastasis. This review systematically summarizes the origin and regulatory mechanisms of platelet PD-L1 （pPD-L1） and proposes a triple-inhibition model of immune evasion mediated by pPD-L1. Furthermore， it highlights the critical role of pPD-L1 as a liquid biopsy biomarker in reversing resistance to immune checkpoint inhibitors （ICIs） and suppressing hematogenous tumor metastasis， providing a theoretical basis for precision therapies targeting pPD-L1.

Key words: platelets, programmed death-ligand 1, immune evasion, hematogenous metastasis, immune checkpoint inhibitors （ICIs）, antiplatelet therapy

CLC Number:

R392.12

Jiacheng JIANG,Jie MA,Wei ZHU. Immunosuppressive effects and targeted therapeutic strategies of platelet-derived PD-L1 in hematogenous tumor metastasis[J]. The Journal of Practical Medicine, 2026, 42(15): 2722-2729.

Figures/Tables 4

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References 43

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特征	小鼠	人	对临床前研究的启示	参考文献
PD-1氨基酸同源性	与人类PD-1的氨基酸序列一致性为59.6%	-	抗体交叉反应性有限	［18］
对治疗性抗体的反应	部分抗体（如atezolizumab）可结合；其他（如durvalumab）不结合	全部可结合	需验证抗体在鼠源的交叉反应性	［19］
小分子/肽类抑制剂	多数不结合mPD-L1	可结合	避免在小鼠模型中筛出假阴性	［19］
PD-1与PD-L1亲和力	较低（相对亲和力设为1）	高（约为小鼠的3.2倍）	人源化小鼠模型更准确评估药物	［20］
PD-1对Shp2招募效率	较低	更高（通过PEQ基序）	小鼠模型可能低估PD-1通路抑制强度	［18］

治疗策略	核心机制	优势	局限性/挑战	参考文献
减少pPD-L1的生成与膜转位	抑制血小板活化/聚集，减少pPD-L1上调及tPD-L1诱导	老药新用，安全性相对明确；临床转化快	出血风险；最佳联合方案未定；需前瞻性临床试验验证	［12-13，33］
直接削弱pPD-L1的免疫抑制功能	化学偶联anti-PD-L1并吸附光热剂；术后局部释放	肿瘤归巢；可联合光热治疗	制备复杂；储存期短；个体差异	［10，34］
清除pPD-L1的细胞载体	cRGD纳米颗粒靶向肿瘤相关血小板，诱导凋亡	精准干预，避免全身血小板耗竭	需验证TAPs特异性标志物；长期安全性	［36］
仿生替代pPD-L1介导的靶向功能	血小板膜包裹纳米内核，继承靶向和免疫逃逸功能	无活细胞储存问题；易于规模化	膜提取及涂层工艺需标准化；体内稳定性待优化	［37］

Immunosuppressive effects and targeted therapeutic strategies of platelet-derived PD-L1 in hematogenous tumor metastasis

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