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.
- Kirfel, J.
- Kümpers, C. C.
- Fähnrich, A.
- Heidel, C.
- Jokic, M.
- Vlasic, I.
- Marwitz, S.
- Goldmann, T.
- Pasternack, H.
- Bohnet, S.
- Jonigk, D.
- Kühnel, M. P.
- Offermann, A.
- Busch, H.
- Perner, S.
Keywords
- cold
- hot
- immune phenotype
- lung adenocarcinoma (LUAD)
- programmed cell death-ligand 1 (PD-L1)
- protein
- transcriptome
- of the study
- in the collection, analyses, or interpretation of data
- in the writing
- of the manuscript, or in the decision to publish the results.
