Gene landscape and correlation between B-cell infiltration and programmed death ligand 1 expression in lung adenocarcinoma patients from The Cancer Genome Atlas data set

Abstract

Tumor-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.

The Risks and Benefits of Immune Checkpoint Blockade in Anti-AChR Antibody-Seropositive Non-Small Cell Lung Cancer Patients

“…The mIHC analysis has been shown to capture multidimensional data related to tissue architecture, spatial distribution of multiple cell phenotypes, and co-expression of signaling [18,19]. A high density of tumor-infiltrating CD8+ T cells and CD20+ B cells has been shown to correlate with prolonged survival in patients with a wide variety of human cancers including lung cancer [20,21,22]. Regulatory T cells (Tregs) have immunosuppressive activity and play a critical role in maintaining immune homeostasis and negatively regulating anti-tumor immune responses [23,24,25].…”

Development of an immune-related gene pairs signature for predicting clinical outcome in lung adenocarcinoma

“…Several studies have revealed that macrophages M1 could promote LUAD cells proliferation, invasion and metastasis [22][23][24] and an increased density of macrophages M1 in TME was associated with poor prognosis in LUAD [25,26], which was in accord with the nding in this study. Previous researches demonstrated accumulating memory B cells were strongly correlated with favorable clinical outcomes in various tumors [27]. In TME, B cells could produce antibodies and present antigen to regulate innate immunity and promote antigen-speci c immune responses to repress tumor development [28][29][30].…”

Development of an Immune-Related Gene Pairs Signature for Predicting Clinical Outcome in Lung Adenocarcinoma

“…Several studies have revealed that macrophages M1 could promote LUAD cells proliferation, invasion and metastasis [22][23][24] and an increased density of macrophages M1 in TME was associated with poor prognosis in LUAD [25,26], which was in accord with the nding in this study. Previous researches demonstrated accumulating memory B cells were strongly correlated with favorable clinical outcomes in various tumors [27]. In TME, B cells could produce antibodies and present antigen to regulate innate immunity and promote antigen-speci c immune responses to repress tumor development [28][29][30].…”