The most prevalent histological type of non-small cell lung cancer (NSCLC) is adenocarcinoma. The WHO classifies this tumor into subtypes according to the predominant growth pattern such as lepidic, acinar, papillary, solid or micropapillary, each harboring specific molecular features. NSCLC adenocarcinoma heterogeneity is discussed to be a reason for therapy failure using targeted therapy or immune checkpoint inhibitors. For successful therapy of immune checkpoint inhibitors the expression and distribution of the involved immune checkpoint proteins is essential. Therefore, we aimed to investigate the distribution of five prominent immune checkpoint proteins in regard of the histological growth patterns of lung adenocarcinoma. We performed immunohistochemical staining of 84 tumor segments from 22 resected tumor samples to evaluate the expression of PD-L1, PD-1, Nectin-2, PVR, and TIGIT in distinct growth patterns of lung adenocarcinoma. We determined a distinct heterogeneity between and within different tumor segments regarding morphological growth patterns. Furthermore, expression of immune checkpoint proteins varied between different growth pattern areas as well as within one distinct growth pattern. Expression of PVR was significantly higher in solid compared to acinar growth pattern (p= 0.00736). Of note, we detected TIGIT not only on tumor infiltrating lymphocytes but also on tumor cells, whereas non-neoplastic lung tissue was consistently TIGIT-negative. The immune checkpoint protein distribution in histologic subtypes of pulmonary adenocarcinoma displays an considerable intra- and intertumoral heterogeneity implying the requirement of either a multiregion or an adjusted analysis when determining the expression status of PD-1:PD-L1 and the TIGIT:PVR/Nectin-2 checkpoint proteins as predictive markers.

非小细胞肺癌 (NSCLC) 最普遍的组织学类型是腺癌。WHO 根据主要的生长模式将这种肿瘤分为亚型，如鳞状、腺泡状、乳头状、实性或微乳头状，每一种都具有特定的分子特征。NSCLC 腺癌异质性被认为是使用靶向治疗或免疫检查点抑制剂治疗失败的一个原因。对于免疫检查点抑制剂的成功治疗，所涉及的免疫检查点蛋白的表达和分布是必不可少的。因此，我们旨在研究五种主要免疫检查点蛋白在肺腺癌组织学生长模式方面的分布。我们对来自 22 个切除肿瘤样本的 84 个肿瘤节段进行了免疫组织化学染色，以评估 PD-L1、PD-1、Nectin-2、PVR 和 TIGIT 在肺腺癌不同生长模式中的表达。我们确定了不同肿瘤节段之间和内部关于形态学生长模式的明显异质性。此外，免疫检查点蛋白的表达在不同的生长模式区域之间以及在一种不同的生长模式内有所不同。与腺泡生长模式相比，PVR 在实体中的表达显着更高 (p = 0.00736)。值得注意的是，我们不仅在肿瘤浸润淋巴细胞上检测到 TIGIT，还在肿瘤细胞上检测到 TIGIT，而非肿瘤性肺组织始终呈 TIGIT 阴性。