Thoracic Surgery Laboratory, Department of Thoracic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Wuhan, 430030, China.
Department of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
J Cancer Res Clin Oncol. 2023 Jul;149(7):3775-3788. doi: 10.1007/s00432-022-04289-3. Epub 2022 Aug 20.
Ground glass opacity featured lung adenocarcinomas (GGO-LUAD) display more indolent biological behavior than solid nodule featured lung adenocarcinomas (SN-LUAD) and have an excellent prognosis. However, the cellular immune characteristics of GGO-LUAD remain poorly understood.
Immunohistochemistry technique was performed to stain related immune markers (CD8, CD103, CD20, CD138, CD4, FOXP3, CD68, CD163, PD-1 and PD-L1) and TGF-β from 15 patients with pure GGO-LUAD and 15 patients with SN-LUAD tissue sections (Paired cohort), and then, the related markers with significant differences were verified on 10 patients (Verified cohort) with both pure GGO-LUAD and SN-LUAD. For localization analysis of CD68 + tumor-associated macrophages (TAMs) and FOXP3 + Terg cells in tumor areas, pure GGO-LUAD and SN-LUAD were also stained for simultaneous detection of pan-CK, CD68 and FOXP3 by multiplex immunofluorescence.
In the Paired cohort, compared with SN-LUAD, only the infiltration of TAMs and Treg cells was significantly lower in GGO-LUAD. The infiltration of the remaining immune cells including CD8 + T cells, CD4 + T cells, CD103 + T cells, CD20 + B cells and CD138 + Plasma cells in GGO-LUAD, although relatively low, was not significantly different. Meanwhile, the expression of TGF-β was significantly higher in SN-LUAD. And the above results have also been confirmed in the Verified cohort. Moreover, there was no significantly difference in PD-L1 expression in GGO-LUAD compared to SN-LUAD both in the Paired cohort and Verified cohort.
GGO-LUAD demonstrates an overall less active immune landscape as compared with SN-LUAD. TAMs and TGF-β may play an important role in the progression of GGO-LUAD. More importantly, PD-L1 expression in GGO-LUAD is comparable to that in SN-LUAD, indicating that there may be other reasons for the insensitivity of GGO-LUAD to immunotherapy.
磨玻璃密度特征的肺腺癌（GGO-LUAD）比实体结节特征的肺腺癌（SN-LUAD）表现出更惰性的生物学行为，预后良好。然而，GGO-LUAD 的细胞免疫特征仍知之甚少。
对 15 例纯 GGO-LUAD 和 15 例 SN-LUAD 组织切片（配对队列）的相关免疫标志物（CD8、CD103、CD20、CD138、CD4、FOXP3、CD68、CD163、PD-1 和 PD-L1）进行免疫组织化学染色，然后在 10 例同时存在纯 GGO-LUAD 和 SN-LUAD 的患者（验证队列）中验证具有显著差异的相关标志物。为了分析肿瘤区域中 CD68+肿瘤相关巨噬细胞（TAMs）和 FOXP3+Terg 细胞的定位，还对纯 GGO-LUAD 和 SN-LUAD 进行了多色免疫荧光染色，同时检测 pan-CK、CD68 和 FOXP3。
在配对队列中，与 SN-LUAD 相比，GGO-LUAD 中 TAMs 和 Treg 细胞的浸润明显较低。GGO-LUAD 中剩余免疫细胞（包括 CD8+T 细胞、CD4+T 细胞、CD103+T 细胞、CD20+B 细胞和 CD138+浆细胞）的浸润虽然相对较低，但无显著差异。同时，SN-LUAD 中 TGF-β 的表达明显较高。验证队列也证实了上述结果。此外，在配对队列和验证队列中，GGO-LUAD 中 PD-L1 的表达与 SN-LUAD 相比均无显著差异。
与 SN-LUAD 相比，GGO-LUAD 表现出总体上更不活跃的免疫景观。TAMs 和 TGF-β 可能在 GGO-LUAD 的进展中发挥重要作用。更重要的是，GGO-LUAD 中 PD-L1 的表达与 SN-LUAD 相当，表明 GGO-LUAD 对免疫治疗不敏感可能有其他原因。
