PD-L1 Dependent Immunogenic Landscape in Hot Lung Adenocarcinomas Identified by Transcriptome Analysis

Kirfel, Jutta; Charlotte Kümpers, Christiane; Fähnrich, Anke; Heidel, Carsten; Jokić, Mladen; Vlašić, Ignacija; Marwitz, Sebastian; Goldmann, Torsten; Pasternack, Helen; Bohnet, Sabine; Jonigk, Danny; Kühnel, Mark P; Offermann, Anne; Busch, Hauke; Perner, Sven (2021) PD-L1 Dependent Immunogenic Landscape in Hot Lung Adenocarcinomas Identified by Transcriptome Analysis. Cancers, 13 (18). ISSN 2072-6694

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Abstract

Background: Lung cancer is the most frequent cause of cancer-related deaths worldwide. The clinical development of immune checkpoint blockade has dramatically changed the treatment paradigm for patients with lung cancer. Yet, an improved understanding of PD-1/PD-L1 checkpoint blockade- responsive biology is warranted. Methods: We aimed to identify the landscape of immune cell infiltration in primary lung adenocarcinoma (LUAD) in the context of tumoral PD-L1 expression and the extent of immune infiltration ("hot" vs. "cold" phenotype). The study comprises LUAD cases (n = 138) with "hot" (≥150 lymphocytes/HPF) and "cold" (<150 lymphocytes/HPF) tumor immune phenotype and positive (>50%) and negative (<1%) tumor PD-L1 expression, respectively. Tumor samples were immunohistochemically analyzed for expression of PD-L1, CD4, and CD8, and further investigated by transcriptome analysis. Results: Gene set enrichment analysis defined complement, IL-JAK-STAT signaling, KRAS signaling, inflammatory response, TNF-alpha signaling, interferon-gamma response, interferon-alpha response, and allograft rejection as significantly upregulated pathways in the PD-L1-positive hot subgroup. Additionally, we demonstrated that STAT1 is upregulated in the PD-L1-positive hot subgroup and KIT in the PD-L1-negative hot subgroup. Conclusion: The presented study illustrates novel aspects of PD-L1 regulation, with potential biological relevance, as well as relevance for immunotherapy response stratification.

Item Type:	Article
Uncontrolled Keywords:	cold ; hot ; immune phenotype ; lung adenocarcinoma (LUAD) ; programmed cell death-ligand 1 (PD-L1) ; protein ; transcriptome
Subjects:	BIOMEDICINE AND HEALTHCARE > Basic Medical Sciences
Divisions:	Division of Molecular Medicine
Depositing User:	Kristina Ciglar
Date Deposited:	04 Feb 2022 09:44
URI:	http://fulir.irb.hr/id/eprint/6961
DOI:	10.3390/cancers13184562

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