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Article Open Access

T cell exhaustion‑related gene CD79B predicts prognosis, inhibits malignant progression and promotes tumor‑associated macrophage M1‑like polarization in lung adenocarcinoma

  • Authors:
    • Xia Wu
    • Chunhui Qu
    • Yiting Ouyang
    • Lifang Yang
    • Wuzhong Jiang
  • View Affiliations / Copyright

    Affiliations: Department of Pathology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China, Cancer Research Institute, School of Basic Medicine Science, Central South University, Changsha, Hunan 410078, P.R. China, Department of Oncology, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China
    Copyright: © Wu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 144
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    Published online on: August 25, 2025
       https://doi.org/10.3892/or.2025.8977
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Abstract

Lung adenocarcinoma (LUAD) is one of the most common malignancies in the lung. T cell exhaustion (TEX) is an important immune escape mechanism that may be targeted to improve tumor immunotherapy. The present study investigated TEX‑related genes in the tumor microenvironment to predict the prognosis of patients with LUAD. Data from 516 patients with LUAD were collected from The Cancer Genome Atlas database and classified them into TEX‑C1 and TEX‑C2 by unsupervised clustering based on the TEX‑related genes. Compared with TEX‑C1, TEX‑C2 cluster had worse prognosis, with shorter overall and progression‑free survival. Functional analysis revealed that upregulated genes in the TEX‑C2 cluster were significantly enriched in tumor immune‑ and metabolism‑related pathways. TEX‑C2 cluster had a poor immune checkpoint blockade (ICB) response and a shorter survival after ICB treatment by Tumor Immune Dysfunction and Exclusion algorithm. A prognostic TEX‑related gene signature was constructed for patients with LUAD by Least Absolute Shrinkage and Selection Operator regression analysis. B cell antigen receptor complex‑associated protein β chain (CD79B) was considered an independent prognostic indicator; in the clinical correlation analysis, the effect of CD79B on prognosis was associated with advanced lung cancer, advanced age, female sex and patients with history of smoking. The overexpression of CD79B was associated with more infiltration of CD8+ T cells, M1 macrophages (the classically activated type 1, pro‑inflammatory type), and less infiltration of M0 (undifferentiated) and M2 macrophages (the alternatively activated type 2, anti‑inflammatory type) by CIBERSORT algorithm, which was also significantly correlated with gene markers of innate and adaptive immune cells, and higher levels of immune checkpoint genes. Upregulation of CD79B could inhibit the proliferation, migration and invasion capabilities and promote the apoptosis of LUAD cells, and induce M1‑like tumor‑associated macrophage (TAM) polarization. In conclusion, patients with LUAD in the TEX‑C2 cluster had worse prognosis and adverse immune microenvironment. CD79B may be a potential prognostic indicator, which could inhibit malignant progression of LUAD cells and induce M1‑like TAM polarization.
View Figures

Figure 1

Cluster and survival analysis of
TEX-related genes in patients with lung adenocarcinoma. (A)
Unsupervised consensus cluster analysis identifying two clusters
(k=2). (B) Heatmap of TEX-related genes in the two clusters. (C)
mRNA expression of TEX-related genes between clusters. Kaplan-Meier
survival analysis of (D) overall and (E) progression-free survival
between TEX clusters. ***P<0.001. TEX-C, T cell exhaustion
cluster; CD79B, B cell Antigen Receptor Complex-Associated Protein
Beta Chain; DUSP, dual Specificity Phosphatase; MTHFD,
Methylenetetrahydrofolate Dehydrogenase; OGFR, Opioid Growth Factor
Receptor; SPON, Spondin; BANK, B Cell Scaffold Protein With Ankyrin
Repeats; CXCL, C-X-C Motif Chemokine Ligand; CCL, C-C Motif
Chemokine Ligand; DRAM, DNA Damage Regulated Autophagy Modulator;
LITAF, Lipopolysaccharide Induced TNF Factor;, HR, Hazard Ratio;
CI, Confidence Interval.

Figure 2

Differential gene expression and gene
enrichment analysis of TEX-based clusters in patients with lung
adenocarcinoma. (A) Heatmap of differentially expressed genes
between TEX clusters, (B) Volcano plot displays the magnitude of
gene expression changes (fold change) and the significance of
changes (P-value). Functional enrichment analysis includes the KEGG
pathway enrichment results (C) and GO term enrichment results (D)
for differentially up- or downregulated genes between the two TEX
clusters. TEX-C, T cell exhaustion cluster; GO, Gene Ontology;
KEGG, Kyoto Encyclopedia of Genes and Genomes.

Figure 3

Tumor immune microenvironment
analysis of TEX-based clusters in patients with lung
adenocarcinoma. (A) Infiltration of immune cells between TEX
clusters was analyzed using the CIBERSORT algorithm. (B) mRNA
expression of PD-L1 between TEX clusters. (C) Heatmap of
correlation between PD-L1 and TEX-related genes. Blue, positive;
red, negative; the darker the color, the stronger the association.
(D) TIDE scores in TEX clusters. *P<0.05, **P<0.01,
***P<0.001 and ****P<0.0001. TEX-C, T cell exhaustion
cluster; TIDE, Tumor Immune Dysfunction and Exclusion; CD79B, B
cell Antigen Receptor Complex-Associated Protein Beta Chain; DUSP,
Dual Specificity Phosphatase; MTHFD, Methylenetetrahydrofolate
Dehydrogenase; OGFR, Opioid Growth Factor Receptor; SPON, Spondin;
BANK, B Cell Scaffold Protein With Ankyrin Repeats; CXCL, C-X-C
Motif Chemokine Ligand; CCL, C-C motif chemokine ligand; DRAM, DNA
Damage Regulated Autophagy Modulator; LITAF, Lipopolysaccharide
Induced TNF Factor; PD-L1, Programmed Cell Death 1 Ligand 1; NK,
natural killer cell.

Figure 4

Construction of the prognostic
TEX-related gene signature in patients with LUAD. (A) Prognostic
analysis of the TEX-related gene signature in patients with LUAD.
The patients were divided into low- and high-risk groups using
median risk score (1.487) as the cutoff value. (B) Kaplan-Meier
analysis of overall survival between low- and high-risk groups. (C)
Uni- and (D) multivariate Cox overall survival analyses of the
prognostic TEX-related genes and other clinicopathological factors
in patients with LUAD. (E) Nomogram based on the results of the
multivariate analysis to predict the 1-, 3- and 5-year overall
survival of patients with LUAD. TEX, T cell exhaustion; LUAD, lung
adenocarcinoma; CD79B, B cell Antigen Receptor Complex-Associated
Protein Beta Chain; DRAM, DNA damage Regulated Autophagy Modulator;
DUSP, Dual Specificity Phosphatase; MTHFD,
Methylenetetrahydrofolate Dehydrogenase; SPON, Spondin; pro,
probability.

Figure 5

Prognosis analysis between CD79B
expression and clinical data in patients with LUAD. The patients
were divided into CD79B-low and -high groups. Kaplan-Meier survival
analysis of (A) overall and (B) progression-free survival between
CD79B-low and -high groups. Association between CD79B expression
and prognosis in patients with LUAD and (C) stage III, (D) age
>65 years, (E) female sex and (F) smoking history. CD79B, B cell
antigen receptor complex-associated protein Beta Chain; LUAD, lung
adenocarcinoma; HR, Hazard Ratio; CI, Confidence Interval.

Figure 6

Tumor immune microenvironment
analysis of CD79B expression in patients with lung adenocarcinoma.
(A) Correlation between CD79B expression and immune cell levels was
analyzed using Spearman's correlation. (B) Infiltration of immune
cells between CD79B-low and -high groups was analyzed using the
CIBERSORT algorithm. Correlation between CD79B and markers of (C)
innate and (D) adaptive immune cells. (E) mRNA expression levels of
immune checkpoint genes between CD79B-low and -high groups.
*P<0.05, **P<0.01, ***P<0.001. CD79B, B cell Antigen
Receptor Complex-Associated Protein Beta Chain; NK, natural killer
cell; CTLA, Cytotoxic T-Lymphocyte Associated Protein 4; HAVCR,
Hepatitis A Virus cellular receptor 1; LAG, Lymphocyte Activating
3; PDCD1LG2, Programmed Cell Death 1 Ligand 2; TIGIT, T Cell
Immunoreceptor with Ig and ITIM Domains; SIGLEC, Sialic Acid
Binding Ig Like Lectin.

Figure 7

Survival analysis between CD79B
expression and driver gene mutations in patients with lung
adenocarcinoma. Overall survival of patients with mut or WT (A)
KRAS, (B) EGFR, (C) BRAF, (D) ALK and (E) TP53 between CD79B-low
and -high groups. CD79B, B-Cell Antigen Receptor Complex-Associated
Protein Beta Chain; ALK, Anaplasticlymphoma Kinase; mut, mutant;
HR, Hazard Ratio; CI, Confidence Interval; WT, widetype.

Figure 8

Prediction of therapeutic drug
sensitivity based on CD79B expression in patients with LUAD. The
distribution of IC50 scores of LUAD chemotherapy and targeted drugs
between CD79B- and CD79B-high groups. *P<0.05, **P<0.01 and
****P<0.0001. CD79B, B-Cell Antigen Receptor Complex-Associated
Protein Beta Chain; LUAD, lung adenocarcinoma; ns, not significant;
IC50, half-maximal inhibitory concentration.

Figure 9

CD79B inhibits proliferation,
migration and invasion and promotes apoptosis of LUAD cells, and
induces M1-like tumor-associated macrophage polarization in
vitro. mRNA and protein expression of CD79B were detected by
(A) qPCR and (B) western blotting in normal lung epithelial HBE and
LUAD cells. A549 cells were transfected with the CD79B-OE plasmid
and mRNA and protein expression of CD79B were detected by (C) qPCR
and (D) western blotting. (E) Cell viability was detected by Cell
Counting Kit 8 assay. (F) Flow cytometry was used to analyze cell
apoptosis. (G) Scratch assay was used to detect cell migration. (H)
Transwell assay was used to analyze cell migration and invasion
ability. (I) M0 macrophage THP-1 cells were co-culture with A549
cells, and the mRNA levels of M1/M2 marker genes were detected by
qPCR after 48 h. **P<0.01, ***P<0.001 and ****P<0.0001.
CD79B, B-Cell Antigen Receptor Complex-Associated Protein Beta
Chain; LUAD, lung adenocarcinoma; q, quantitative; OE,
Over-Expression; ns, not significant; Vec, Vector; iNOS. Nitric
Oxide Synthase, Inducible.
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Copy and paste a formatted citation
Spandidos Publications style
Wu X, Qu C, Ouyang Y, Yang L and Jiang W: T cell exhaustion‑related gene CD79B predicts prognosis, inhibits malignant progression and promotes tumor‑associated macrophage M1‑like polarization in lung adenocarcinoma. Oncol Rep 54: 144, 2025.
APA
Wu, X., Qu, C., Ouyang, Y., Yang, L., & Jiang, W. (2025). T cell exhaustion‑related gene CD79B predicts prognosis, inhibits malignant progression and promotes tumor‑associated macrophage M1‑like polarization in lung adenocarcinoma. Oncology Reports, 54, 144. https://doi.org/10.3892/or.2025.8977
MLA
Wu, X., Qu, C., Ouyang, Y., Yang, L., Jiang, W."T cell exhaustion‑related gene CD79B predicts prognosis, inhibits malignant progression and promotes tumor‑associated macrophage M1‑like polarization in lung adenocarcinoma". Oncology Reports 54.5 (2025): 144.
Chicago
Wu, X., Qu, C., Ouyang, Y., Yang, L., Jiang, W."T cell exhaustion‑related gene CD79B predicts prognosis, inhibits malignant progression and promotes tumor‑associated macrophage M1‑like polarization in lung adenocarcinoma". Oncology Reports 54, no. 5 (2025): 144. https://doi.org/10.3892/or.2025.8977
Copy and paste a formatted citation
x
Spandidos Publications style
Wu X, Qu C, Ouyang Y, Yang L and Jiang W: T cell exhaustion‑related gene CD79B predicts prognosis, inhibits malignant progression and promotes tumor‑associated macrophage M1‑like polarization in lung adenocarcinoma. Oncol Rep 54: 144, 2025.
APA
Wu, X., Qu, C., Ouyang, Y., Yang, L., & Jiang, W. (2025). T cell exhaustion‑related gene CD79B predicts prognosis, inhibits malignant progression and promotes tumor‑associated macrophage M1‑like polarization in lung adenocarcinoma. Oncology Reports, 54, 144. https://doi.org/10.3892/or.2025.8977
MLA
Wu, X., Qu, C., Ouyang, Y., Yang, L., Jiang, W."T cell exhaustion‑related gene CD79B predicts prognosis, inhibits malignant progression and promotes tumor‑associated macrophage M1‑like polarization in lung adenocarcinoma". Oncology Reports 54.5 (2025): 144.
Chicago
Wu, X., Qu, C., Ouyang, Y., Yang, L., Jiang, W."T cell exhaustion‑related gene CD79B predicts prognosis, inhibits malignant progression and promotes tumor‑associated macrophage M1‑like polarization in lung adenocarcinoma". Oncology Reports 54, no. 5 (2025): 144. https://doi.org/10.3892/or.2025.8977
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