ArticleOncoimmunology2016
Upregulation of PD-L1 by EML4-ALK fusion protein mediates the immune escape in ALK positive NSCLC: Implication for optional anti-PD-1/PD-L1 immune therapy for ALK-TKIs sensitive and resistant NSCLC patients.
Article in Oncoimmunology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
89 citing papers in PubMed, 2 syntheses or guidelines pooled it, 131 citations in OpenAlex.
- Current status and challenges of immunotherapy in ALK rearranged NSCLC.Frontiers in oncology · 2022Pooled it
- Immune-checkpoint inhibitor plus chemotherapy versus conventional chemotherapy for first-line treatment in advanced non-small cell lung carcinoma: a systematic review and meta-analysis.Journal for immunotherapy of cancer · 2018Pooled it
- Clinical significance of ≥ 50% PD-L1 expression with the SP263 monoclonal antibody in non-small cell lung cancer patients.Thoracic cancer · 2019Trial
- DTX3 promotes anti-tumor immunity by inducing PD-L1 ubiquitination and is suppressed by p65/miR-222 in bladder cancer.Oncogene · 2026Article
- Transformation of ALK-translocated lung adenocarcinoma to LCNEC under alectinib treatment - a case report and mini-review.The oncologist · 2026Review
- The prognostic significance of the IASLC grading system in ALK-positive invasive non-mucinous adenocarcinoma of the lung: correlation with clinicopathological features.The journal of pathology. Clinical research · 2026Article
- Brain metastases from non-small cell lung cancer: molecular subtypes and emerging CNS-directed precision therapies.Frontiers in oncology · 2026Review
- A translational study on the survival and molecular mechanism of PD-L1 expression in EGFR-mutant NSCLC treated with osimertinib.iScience · 2025Article
- Myeloid-derived suppressor cells modulation in the context of tumor microenvironment for gastric cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Review
- Single-cell RNA profiling reveals an immunosuppressive microenvironment inTranslational lung cancer research · 2025Article
- The Role of Immune Checkpoint Inhibitors in Cancer Therapy: Mechanism and Therapeutic Advances.MedComm · 2025Review
- Fusion genes in cancers: Biogenesis, functions, and therapeutic implications.Genes & diseases · 2025Review
- Case report: Alectinib-associated intestinal ulceration and colitis in a patient with non-small cell lung cancer and effective treatment with Mesalazine.Pathology oncology research : POR · 2025Article
- Long-term survival after ALK-TKI resistance through immunotherapy combined with chemotherapy in ALK-positive non-small cell lung cancer: a case report.Frontiers in oncology · 2025Article
- Ivonescimab combined with chemotherapy shows promising efficacy in an ALK fusion-positive lung adenocarcinoma patient with ALK-TKI resistance: a case report.Frontiers in oncology · 2025Article
- New advances in understanding the mechanisms and treatment challenges of ALK-targeted therapy resistance in lung cancer.Cancer drug resistance (Alhambra, Calif.) · 2025Review
- Immunotherapy Following Anaplastic Lymphoma Kinase Inhibitor Therapy for Patients with Anaplastic Lymphoma Kinase‑Positive Non‑small Cell Lung Cancer in Japan.Targeted oncology · 2025Article
- Avelumab in Combination With Lorlatinib or Crizotinib in Patients With Previously Treated Advanced NSCLC: Phase 1b/2 Results From the JAVELIN Lung 101 Trial.JTO clinical and research reports · 2024Article
- Association of PD-L1 expression with driver gene mutations and clinicopathological characteristics in non-small cell lung cancer: A real-world study of 10 441 patients.Thoracic cancer · 2024Article
- Targeting MDM2 in malignancies is a promising strategy for overcoming resistance to anticancer immunotherapy.Journal of biomedical science · 2024Review
29 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Driver mutations were reported to upregulate programmed death-ligand 1 (PD-L1) expression. However, how PD-L1 expression and immune function was affected by ALK-TKIs and anti-PD-1/PD-L1 treatment in ALK positive non-small-cell lung cancer (NSCLC) remains poorly understood. In the present study, western-blot, real-time PCR, flow cytometry and immunofluorescence were employed to explore how PD-L1 was regulated by ALK fusion protein. ALK-TKIs and relevant inhibitors were used to identify the downstream signaling pathways involved in PD-L1 regulation. Cell apoptosis, viability and Elisa test were used to study the immune suppression by ALK activation and immune reactivation by ALK-TKIs and/or PD-1 blocking in tumor cells and DC-CIK cells co-culture system. We found that PD-L1 expression was associated with EGFR mutations and ALK fusion genes in NSCLC cell lines. Over-expression of ALK fusion protein increased PD-L1 expression. PD-L1 mediated by ALK fusion protein increased the apoptosis of T cells in tumor cells and DC-CIK cells co-culture system. Inhibiting ALK by sensitive TKIs could enhance the production of IFNγ. Anti-PD-1 antibody was effective in both crizotinib sensitive and resistant NSCLC cells. Synergistic tumor killing effects were not observed with ALK-TKIs and anti-PD-1 antibody combination in co-culture system. ALK-TKIs not only directly inhibited tumor viability but also indirectly enhanced the antitumor immunity via the downregulation of PD-L1. Anti-PD-1/PD-L1 antibodies could be an optional therapy for crizotinib sensitive, especially crizotinib resistant NSCLC patients with ALK fusion gene. Combination of ALK-TKIs and anti-PD-1/PD-L1 antibodies treatment for ALK positive NSCLC warrants more data before moving into clinical practice.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.