• Kuo-Hao Ho, Chih-Ju Chang, Tzu-Wen Huang, Chwen-Ming Shih, Ann-Jeng Liu, Peng-Hsu Chen, Kur-Ta Cheng, and Ku-Chung Chen.
• Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan.
• Plos One. 2018 Jan 1; 13 (12): e0208459.

AbstractTumor-infiltrating lymphocytes are related to positive clinical prognoses in numerous cancer types. Programmed death ligand 1 (PD-L1), a mediator of the PD-1 receptor, plays an inhibitory role in cancer immune responses. PD-L1 upregulation can impede infiltrating T-cell functions in lung adenocarcinoma (LUAD), a lung cancer subtype. However, associations between the expression of PD-L1 and infiltration of B cells (a major immunoregulatory cell) remain unknown. Therefore, we investigated the role of infiltrating B cells in LUAD progression and its correlation with PD-L1 expression. The Cancer Genome Atlas (TCGA) LUAD data set was used to explore associations among B-cell infiltration, PD-L1 expression, clinical outcome, and gene landscape. Gene set enrichment analysis was used to explore putative signaling pathways and candidate genes. The drug enrichment analysis was used to identify candidate genes and the related drugs. We found that high B-cell infiltration was correlated with better prognoses; however, PD-L1 may interfere with the survival advantage in patients with high B-cell infiltration. The gene landscape was characterized comprehensively, with distinct PD-L1 levels in cell populations with high B-cell infiltration. We obtained five upregulated signaling pathways from the gene landscape: apoptosis, tumor necrosis factor (TNF)-α signaling via nuclear factor (NF)-κB, apical surface, interferon-α response, and KRAS signaling. Moreover, four candidate genes and their related target drugs were also identified, namely interleukin-2β receptor (IL2RB), IL-2γ receptor (IL2RG), Toll-like receptor 8 (TLR8), and TNF. These findings suggest that tumor-infiltrating B cells could act as a clinical factor in anti-PD-L1 immunotherapy for LUAD.

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