Background: This study aims at screening and validation of prospective genetic signature for lung adenocarcinoma (LUAD) prognosis and treatment.
Methods: The immune-related genes (IRGs) were obtained from The Cancer Genome Atlas (TCGA) dataset where a total of 535 LUAD and 59 control samples were included. A risk model was then developed for the risk stratification of LUAD patients. The immune cell infiltration, clinical outcomes, and the therapeutic efficacy of programmed cell death protein 1 (PD-1) and its ligand (PD-L1) blockade were compared between high and low-risk groups. Gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) were used to explore the biological processes and signalling pathways associated with the IRGs. Finally, IRGs mRNA levels were assayed by reverse transcription quantitative real-time PCR (RT-qPCR) in LUAD and relevant cell lines.
Results: Two IRGs, P2RX1 (purinergic receptor P2X 1) and PCP4 (Purkinje cell protein 4), were screened from a module that possesses the highest correlation with plasma cells. RT-qPCR verified the expression of the two IRGs in plasmacytoma cell RPMI 8226 but not in LUAD cells. A higher risk score is associated with a lower infiltration of immune cells. Kaplan-Meier and nomogram analysis showed that the high-risk group has a lower survival rate than the low-risk cohort. Furthermore, the high-risk group had a worse response rate to PD-L1/PD-1 blockade. GSVA and GSEA-GO results indicated that a lower risk score is linked to signalling pathways and biological functions promoting immune response and inflammation. In contrast, a higher risk score is associated with signalling cascades promoting tumour growth.
Conclusion: The immune-related prognostic model based on P2RX1 and PCP4 is conducive to predicting the therapeutic response of PD-L1/PD-1 blockade and clinical outcomes of LUAD.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1007/s00432-023-05153-8 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
NI-3201 Is a Bispecific Antibody Mediating PD-L1-Dependent CD28 Co-stimulation on T Cells for Enhanced Tumor Control.
Cancer Immunol Res
January 2025
Light Chain Bioscience - Novimmune SA, Geneva, Switzerland.
Article Synopsis
- Advances in cancer immunotherapy face challenges with patient resistance and relapses, prompting exploration of bispecific antibodies like NI-3201, designed to enhance T-cell activation against tumors.
- NI-3201 works by blocking the PD-L1/PD-1 pathway and providing additional T-cell stimulation through CD28, showing promising in vitro and in vivo results for tumor regression and immune memory.
- Preclinical safety assessments indicate good tolerability, and future studies aim to further investigate NI-3201's potential in improving outcomes for patients with PD-L1+ solid tumors.
Prognostic implications of immune classification based on PD-L1 expression and tumor-infiltrating lymphocytes in endocervical adenocarcinoma.
Transl Oncol
December 2024
Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China; Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou 510060, China. Electronic address:
Background: Endocervical adenocarcinoma (ECA) comprises a heterogeneous group of diseases whose incidence has increased significantly in recent decades. ECA can be histologically classified into human papillomavirus-associated (HPVA) and non-HPVA (NHPVA) types. Given the variability in pathological features and clinical behavior between the subtypes, evaluating their respective immune microenvironments is essential.
View Article and Find Full Text PDFWhile immune-checkpoint blockade (ICB) has revolutionized treatment of metastatic melanoma over the last decade, the identification of broadly applicable robust biomarkers has been challenging, driven in large part by the heterogeneity of ICB regimens and patient and tumor characteristics. To disentangle these features, we performed a standardized meta-analysis of eight cohorts of patients treated with anti-PD-1 (n=290), anti-CTLA-4 (n=175), and combination anti-PD-1/anti-CTLA-4 (n=51) with RNA sequencing of pre-treatment tumor and clinical annotations. Stratifying by immune-high vs -low tumors, we found that surprisingly, high immune infiltrate was a biomarker for response to combination ICB, but not anti-PD-1 alone.
View Article and Find Full Text PDFMethionine restriction promotes the polarization of macrophages towards M1 and the immunotherapy effect of PD-L1/PD-1 blockades by inhibiting the secretion of MIF by gastric carcinoma cells.
Transl Oncol
January 2025
Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi Province, China.
Background: The limited curative effect of PD-L1/PD-1 blockades presents challenges to immunotherapy for advanced gastric cancer. We have found that methionine restriction (MR) enhances the drug resistance of gastric carcinoma cells. We aimed to explore whether MR can enhance the efficacy of PD-L1/PD-1 blockades in gastric cancer.
View Article and Find Full Text PDFEchinacoside inhibits tumor immune evasion by downregulating inducible PD-L1 and reshaping tumor immune landscape in breast and colorectal cancer.
Phytomedicine
December 2024
Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China. Electronic address:
Background: Targeting PD-L1 has become a crucial approach in tumor immunotherapy. Echinacoside (ECH) is a natural compound known for its extensive biological activities, its impact on antitumor immunity remains uncertain.
Purpose: This work was designed to assess the effects of ECH on the PD-L1/PD-1-mediated tumor immune evasion and its underlying mechanisms.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!