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Abstract：
PD-L1 immunohistochemistry (IHC) has become an established method for predicting cancer response to targeted anti-PD1 immunotherapies, including breast cancer (BC). The alternative PD-1 ligand, PD-L2, remains understudied but may be a complementary predictive marker. Prospective analysis of 32 breast cancers revealed divergent expression patterns of PD-L1 and PD-L2. PD-L1-positivity was higher in immune cells than in cancer cells (median = 5.0% vs. 0.0%; p = 0.001), whereas PD-L2-positivity was higher in cancer cells than immune cells (median = 30% vs. 5.0%; p = 0.001). Percent positivity of PD-L1 and PD-L2 were not correlated, neither in cancer cells nor immune cells. Based on a cut-point of ≥1% positivity, ER+ tumors (n = 23) were frequently PD-L2-positive (73.9%), whereas only 40.9% were PD-L1-positive. These data suggest differential control of cellular PD-L1 and PD-L2 expression in BC and a potential role for PD-L2 IHC as a complementary marker to PD-L1 to improve selection of aggressive ER+ BC that may benefit from anti-PD-1 therapy.
摘要：
PD-L1免疫组织化学（IHC）已成为预测癌症对靶向抗PD1免疫疗法的反应的既定方法，包括乳腺癌（BC）。替代的PD-1配体，PD-L2仍未被研究，但可能是一个互补的预测标记。对32例乳腺癌的前瞻性分析显示PD-L1和PD-L2的表达模式不同。免疫细胞中的PD-L1阳性高于癌细胞（中位数=5.0％vs.0.0%；p=0.001)，而PD-L2阳性在癌细胞中高于免疫细胞(中位数=30%vs.5.0%；p=0.001）。PD-L1和PD-L2的阳性百分比不相关，既不存在于癌细胞中，也不存在于免疫细胞中。基于≥1%阳性的临界点，ER+肿瘤（n=23）经常是PD-L2阳性（73.9%），而只有40.9%的PD-L1阳性。这些数据表明BC中细胞PD-L1和PD-L2表达的差异控制以及PD-L2IHC作为PD-L1的互补标志物的潜在作用，以改善可能受益于抗PD-1治疗的侵袭性ER+BC的选择。
