Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China.
Department of Pathology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Science, Jinan, China.
Cancer Immunol Immunother. 2023 Jul;72(7):2015-2027. doi: 10.1007/s00262-023-03380-z. Epub 2023 Feb 4.
To explore the relationship between the spatial interaction of programmed death-ligand 1(PD-L1)-positive tumor cell and T cell with specific functions and the recurrence of non-small cell lung cancer (NSCLC) and optimize prognostic stratification.
This study retrospectively included 104 patients with locally advanced NSCLC who underwent radical surgery. Tissue microarrays were constructed including tumor center (TC) and invasion margin (IM), and CK/CD4/CD8/PD-L1/programmed death-1 (PD-1) was labeled using multiplex immunofluorescence to decipher the counts and spatial distribution of tumor cells and T cells. The immune microenvironment and recurrence stratification were characterized using the Mann-Whitney U test and Cox proportional hazards model.
Compared with the IM, the proportion of tumor cells (especially PD-L1) was increased in the TC, while T cells (especially PD-1) were decreased. An increase in TC PD-1 CD8 T cells promoted relapse (HR = 2.183), while PD-L1 tumor cells alone or in combination with T cells had no predictive value for relapse. In addition, in both TC and IM, CD8 were on average closer to PD-L1 tumor cells than CD4, especially exhausted CD8. The effective density and percentage of PD-1 CD4 T cells interacting with PD-L1 tumor cells in the IM were both associated with recurrence, and the HRs increased sequentially (HRs were 2.809 and 4.063, respectively). Patients with low PD-1CD4 count combined high PD-1CD4 effective density showed significantly poorer RFS compared to those with high PD-1CD4 count combined low PD-1CD4 effective density, in both the TC and IM regions (HRs were 5.810 and 8.709, respectively).
Assessing the relative spatial proximity of PD-1/PD-L1 contributes to a deeper understanding of tumor immune escape and generates prognostic information in locally advanced NSCLC patients.
探索程序性死亡配体 1（PD-L1）阳性肿瘤细胞与具有特定功能的 T 细胞的空间相互作用与非小细胞肺癌（NSCLC）复发之间的关系，并优化预后分层。
本研究回顾性纳入 104 例接受根治性手术的局部晚期 NSCLC 患者。构建组织微阵列，包括肿瘤中心（TC）和侵袭边缘（IM），并使用多重免疫荧光法标记 CK/CD4/CD8/PD-L1/程序性死亡-1（PD-1），以解析肿瘤细胞和 T 细胞的数量和空间分布。采用 Mann-Whitney U 检验和 Cox 比例风险模型对免疫微环境和复发分层进行特征描述。
与 IM 相比，TC 中肿瘤细胞（尤其是 PD-L1）的比例增加，而 T 细胞（尤其是 PD-1）减少。TC PD-1 CD8 T 细胞的增加促进了复发（HR=2.183），而单独的 PD-L1 肿瘤细胞或与 T 细胞联合使用对复发均无预测价值。此外，在 TC 和 IM 中，CD8 平均比 CD4 更接近 PD-L1 肿瘤细胞，尤其是耗竭的 CD8。IM 中 PD-1 CD4 T 细胞与 PD-L1 肿瘤细胞相互作用的有效密度和百分比均与复发相关，且 HR 依次增加（HR 分别为 2.809 和 4.063）。TC 和 IM 中 PD-1CD4 计数低结合 PD-1CD4 有效密度高的患者的 RFS 明显低于 PD-1CD4 计数高结合 PD-1CD4 有效密度低的患者（HR 分别为 5.810 和 8.709）。
评估 PD-1/PD-L1 的相对空间接近度有助于更深入地了解肿瘤免疫逃逸，并为局部晚期 NSCLC 患者提供预后信息。
