Background/Objectives: Vascular endothelial growth factor (VEGF)-A promotes an immunosuppressive tumor microenvironment, potentially affecting the efficacy of anti-programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) antibody therapy. VEGF121and VEGF165, VEGF-A isoforms, promote and inhibit tumor growth, respectively. Additionally, VEGF-A levels differ depending on whether they are measured in serum or plasma. However, whether the serum or plasma levels of total VEGF-A (tVEGF-A) or its isoforms are the most suitable for predicting anti-PD-1/PD-L1 antibody therapy efficacy remains unclear. Methods: Eighty-six patients with non-small-cell lung cancer (NSCLC) who were treated with anti-PD-1/PD-L1 antibody monotherapy between December 2015 and December 2023 were retrospectively enrolled. The association between the serum and plasma levels of tVEGF-A and its isoforms (VEGF121and VEGF165) and treatment outcomes was analyzed. Results: The median progression-free survival (PFS) was 2.9 months, and the objective response rate (ORR) was 23.3%. PFS was significantly shorter in patients with higher tVEGF-A serum levels (≥484.2 pg/mL) than in those without (median PFS 2.1 vs. 3.7 months,p= 0.004). In contrast, plasma tVEGF-A levels could not be used to stratify PFS. Therefore, the serum levels of VEGF-A isoforms were measured. Patients with higher VEGF121serum levels (≥523.5 pg/mL) showed both significantly shorter PFS (median PFS 2.3 vs. 3.3 months,p= 0.022) and a lower ORR (9.7% vs. 30.9%,p= 0.033) than those without. Multivariate Cox and logistic regression analyses showed that higher levels of serum VEGF121were significantly associated with shorter PFS and a lower ORR. Conclusions: Serum VEGF121levels may be useful in predicting anti-PD-1/PD-L1 antibody monotherapy efficacy.
**背景/目的：** 血管内皮生长因子A（VEGF-A）可促进免疫抑制性肿瘤微环境，可能影响抗程序性细胞死亡蛋白1（PD-1）/程序性细胞死亡蛋白配体1（PD-L1）抗体疗法的疗效。VEGF-A亚型VEGF121和VEGF165分别具有促进和抑制肿瘤生长的作用。此外，VEGF-A水平因检测样本（血清或血浆）而异。然而，总VEGF-A（tVEGF-A）或其亚型的血清或血浆水平，何者最适合用于预测抗PD-1/PD-L1抗体疗法的疗效，目前尚不清楚。 **方法：** 本研究回顾性纳入了2015年12月至2023年12月期间接受抗PD-1/PD-L1抗体单药治疗的86例非小细胞肺癌（NSCLC）患者。分析了血清和血浆中tVEGF-A及其亚型（VEGF121和VEGF165）水平与治疗结局之间的关联。 **结果：** 中位无进展生存期（PFS）为2.9个月，客观缓解率（ORR）为23.3%。血清tVEGF-A水平较高（≥484.2 pg/mL）的患者，其PFS显著短于水平较低的患者（中位PFS：2.1个月 vs. 3.7个月，p=0.004）。相比之下，血浆tVEGF-A水平无法用于PFS分层。因此，进一步检测了VEGF-A亚型的血清水平。与血清VEGF121水平较低的患者相比，血清VEGF121水平较高（≥523.5 pg/mL）的患者，其PFS显著更短（中位PFS：2.3个月 vs. 3.3个月，p=0.022），且ORR更低（9.7% vs. 30.9%，p=0.033）。多变量Cox回归和逻辑回归分析显示，较高的血清VEGF121水平与较短的PFS和较低的ORR显著相关。 **结论：** 血清VEGF121水平可能有助于预测抗PD-1/PD-L1抗体单药治疗的疗效。
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