PD-L1 和 PD-L2 的差异表达与非小细胞肺癌中 TILs 和 M2 TAMs 的肿瘤微环境及肿瘤分化相关

To improve the treatment strategy of immune checkpoint inhibitors for non small cell lung cancer (NSCLC), a comprehensive analysis of programmed death ligand (PD L)1 and PD L2 expression is clinically important. The expression of PD L1 and PD L2 on both tumor cells (TCs) and tumor infiltrating immune cells (ICs) was investigated, with respect to tumor infiltrating lymphocytes (TILs) and M2 tumor associated macrophages (TAMs), which are key components of the tumor microenvironment, in 175 patients with resected NSCLC.

The TIL and M2 TAM densities were associated with the expression of PD L1 on the two TCs (both P<0. 0001) and ICs (both P<0. 0001). The TIL and M2 TAM densities were also associated with the expression of PD L2 on both TCs (P=0. 0494 and P=0. 0452, respectively) and ICs (P=0. 0048 and P=0. 0125, respectively).

However, there was no correlation between the percentage of PD L1 positive TCs and the percentage of PD L2 positive TCs (r=0. 019; P=0. 8049). Meanwhile, tumor differentiation was significantly associated with the PD L1 expression on TCs and ICs (P=0. 0002 and P<0. 0001, respectively). By contrast, tumor differentiation was inversely associated with the PD L2 expression on both TCs and ICs (P=0. 0260 and P=0. 0326, respectively).

In conclusion, the combined evaluation of PD L1 and PD L2 expression could be clinically important in the treatment strategy of immune checkpoint inhibitors in patients with NSCLC. In particular, the evaluation of PD L2 expression may be necessary for patients with PD L1 negative NSCLC.