Spatial distribution of immune checkpoint proteins in histological subtypes of lung adenocarcinoma

Abstract

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.

CD155 expression and its clinical significance in non‑small cell lung cancer

“…Next, we showed that CD155-positivity was significantly associated with aggressive cancer behavior such as pleural/vascular invasion and was a significant factor to predict a poor prognosis. Previous clinical studies in NSCLC also showed that CD155-positivity was correlated with a poor prognosis ( 14 , 16 – 21 ). However, characteristics of patients included in previous studies were too heterogenous to draw a definitive conclusion.…”

“…The present study revealed the detailed CD155 expression in lung adenocarcinoma. As the TIGIT/CD155 axis has emerged as a novel therapeutic target in a variety of malignant tumors, several studies on the CD155 expression in NSCLC including lung adenocarcinoma have been reported ( 14 – 21 ). However, no study has previously reported detailed distribution of tumoral CD155 expression.…”

Prognostic impact of PD-L1 and TIGIT expression in non-small cell lung cancer following concurrent chemo-radiotherapy

“…Despite their durable response, ICI monotherapy has a response rate of at most 20%, leading to the development of combinations of ICIs. Basic research reported good prospects for combination therapy with multiple ICIs 3 , 4 , which has also been proven in clinical studies 5 – 8 . In the phase II CITYSCAPE trial, anti-T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif (ITIM) domain (TIGIT) antibody tiragolumab combined with the PD-L1 inhibitor atezolizumab significantly improved the overall response rate compared to anti-PD-L1 monotherapy (37% vs. 21%) (37% vs. 21%) 9 .…”

Update Thoraxpathologie 2021 – Bericht der Arbeitsgemeinschaft

“…Florian Länger (Hannover) gab einen sehr umfassenden Überblick zu interstitiellen Lungenerkrankungen im Säuglings- und Kindesalter, der sicher einen längeren Slot verdient hätte [ 5 ]. Ralf Marienfeld (Ulm) trug die Ergebnisse zur räumlichen Verteilung der Immuncheckpoint-Proteine in unterschiedlichen morphologischen Subtypen von Adenokarzinomen der Lunge vor [ 6 ]. Philip Bischoff (Berlin) berichtete zur Charakterisierung des Tumormikromilieus in Adenokarzinomen der Lunge mittels Einzelzell-RNA-Sequenzierung.…”