骨化蛋白A1（ANXA1）的解离，作为炎症和免疫的调节因子，导致癌症生长和转移。然而，ANXA1是否参与癌症免疫抑制仍不清楚。在这里，我们报告了ANXA1沉默（i）显著降低乳腺癌、肺癌和黑色素瘤细胞中编程细胞死亡配体1（PD-L1）的表达；（ii）促进体外T细胞介导的癌细胞杀伤；以及（iii）通过降低PD-L1的表达并增加CD8+ T细胞的数量和杀伤活性，抑制免疫能力正常的小鼠中的癌症免疫逃逸。在机制上，ANXA1作为聚合酶1（PARP1）和Stat3相互作用的海绵分子发挥作用。具体而言，ANXA1与PARP1的结合减少了PARP1与Stat3的结合，从而降低了Stat3的ADP-核糖基磷酸（poly(ADP-ribosyl)ation）和去磷酸化，从而增加了Stat3的转录活性，导致在多种癌细胞中PD-L1的转录上调表达。在临床样本中，与相应的正常组织相比，骨化蛋白A1和PD-L1的表达在乳腺癌、非小细胞肺癌和皮肤切除黑色素瘤中明显增加，并在癌组织中呈正相关。此外，使用ANXA1和PD-L1蛋白质来预测抗PD-1免疫疗法的疗效和患者预后优于使用单个蛋白质。我们的数据表明，ANXA1通过结合PARP1并上调Stat3诱导的PD-L1表达促进了癌症免疫逃逸，ANXA1是癌症免疫治疗的潜在新靶点，并且ANXA1和PD-L1表达的组合是预测多种癌症中抗PD-1免疫疗法疗效的潜在标志物。

The deregulation of annexin A1 (ANXA1), a regulator of inflammation and immunity, leads to cancer growth and metastasis. However, whether ANXA1 is involved in cancer immunosuppression is still unclear. Here, we report that ANXA1 knockdown (i) dramatically downregulates programmed cell death-ligand 1 (PD-L1) expression in breast cancer, lung cancer, and melanoma cells; (ii) promotes T cell-mediated killing of cancer cells in vitro; and (iii) inhibits cancer immune escape in immune-competent mice via downregulating PD-L1 expression and increasing the number and killing activity of CD8+ T cells. Mechanistically, ANXA1 functioned as a sponge molecule for interaction of PARP1 and Stat3. Specifically, binding of ANXA1 to PARP1 decreased PARP1's binding to Stat3, which reduced poly(ADP-ribosyl)ation and dephosphorylation of Stat3 and thus, increased Stat3's transcriptional activity, leading to transcriptionally upregulated expression of PD-L1 in multiple cancer cells. In clinical samples, expression of ANXA1 and PD-L1 was significantly higher in breast cancer, non-small cell lung cancer, and skin cutaneous melanoma compared to corresponding normal tissues and positively correlated in cancer tissues. Moreover, using both ANXA1 and PD-L1 proteins for predicting efficacy of anti-PD-1 immunotherapy and patient prognosis were superior to using individual proteins. Our data suggest that ANXA1 promotes cancer immune escape via binding PARP1 and upregulating Stat3-induced expression of PD-L1, that ANXA1 is a potential new target for cancer immunotherapy, and combination of ANXA1 and PD-L1 expression is a potential marker for predicting efficacy of anti-PD-1 immunotherapy in multiple cancers.