ArticleFrontiers in immunology2022
Characteristics of the immune microenvironment and their clinical significance in non-small cell lung cancer patients with ALK-rearranged mutation.
Article in Frontiers in immunology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed.
- Influence of oncogenic drivers and signaling pathways on immune checkpoint inhibitor efficacy in NSCLC.Genes & diseases · 2027Review
- High Programmed Death-Ligand 1 Expression is Associated With a Shorter Progression Free Survival in ALK-Rearranged Lung Cancer Patients Treated With First Line Tyrosine Kinase Inhibitors.Clinical lung cancer · 2026Article
- Gilteritinib overcomes second‑generation TKIs resistance in ALK‑rearranged non‑small‑cell lung cancer by inhibiting PD‑L1 and CD8 co‑expression.International journal of molecular medicine · 2026Article
- Identification of ISZ-sTRAIL Protein as a Potent Anticancer Agent for EML4-ALK-Positive Non-Small-Cell Lung Cancer.Molecules (Basel, Switzerland) · 2026Article
- 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
- Individualized duration of adjuvant alectinib therapy and rechallenge efficacy in ALK-positive non-small cell lung cancer: a case report.Frontiers in medicine · 2026Article
- Added value of abdominal CT after treatment of lung cancer.Quantitative imaging in medicine and surgery · 2025Article
- Advances in immunotherapy for driver gene-positive non-small cell lung cancer: a narrative review.Translational lung cancer research · 2025Review
- Prevalence and biological impact of clinically relevant gene fusions in head and neck cancers.NPJ precision oncology · 2025Article
- Efficacy of immunotherapy in advancedTranslational lung cancer research · 2025Article
- The Current State of Tumor Microenvironment-Specific Therapies for Non-Small Cell Lung Cancer.Cancers · 2025Review
- Impact of histopathological subtypes on invasive lung adenocarcinoma: from epidemiology to tumour microenvironment to therapeutic strategies.World journal of surgical oncology · 2025Review
- Ensartinib as a neoadjuvant therapy for stage IIIA non-small cell lung cancer patients with EML4-ALK fusion: a case report and literature review.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
- Radiomic features and tumor immune microenvironment associated with anaplastic lymphoma kinase-rearranged lung adenocarcinoma and their prognostic value.Frontiers in genetics · 2025Article
- Unraveling the Potential of ALK-Targeted Therapies in Non-Small Cell Lung Cancer: Comprehensive Insights and Future Directions.Biomedicines · 2024Review
- High PD-L1 Expression Correlates with an Immunosuppressive Tumour Immune Microenvironment and Worse Prognosis inBiomolecules · 2023Article
- Narrative review: immunotherapy in anaplastic lymphoma kinase (ALK)+ lung cancer-current status and future directions.Translational lung cancer research · 2023Review
- Spoilt for choice: different immunosuppressive potential of anaplastic lymphoma kinase inhibitors for non small cell lung cancer.Frontiers in immunology · 2023Article
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12 authors.
Funding
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Abstract
Background: Although immune checkpoint inhibitors (ICIs) are one of the most important treatments for advanced-stage non-small-cell lung cancer (NSCLC), NSCLC patients with ALK-rearranged usually don't obtain a clinical benefit. The reason may be related to the unique tumor microenvironment (TME). We evaluated the characteristics of immune biomarkers of the TME and their prognostic value in ALK-rearranged NSCLC. Methods: Tumor samples from patients with ALK-rearranged (N = 39) and EGFR- (N = 40)/KRAS- (N = 30) mutated NSCLC were collected. Immunohistochemistry (IHC) was used to assess the expression of 9 tumor immune markers as well as 6 immune markers of tumor-infiltrating cells. To research the TME of ALK-rearranged NSCLC, EGFR/KRAS-positive patients were used as controls. Furthermore, the correlation between the efficacy and prognosis of patients with advanced-stage (IIIC-IV) ALK rearrangements treated with targeted drugs was analyzed in terms of the TME. Results: The proportion of PD-L1+ tumors was lower in ALK-positive NSCLC than in KRAS-positive NSCLC. Besides, the proportion of T cells expressing TIM-3-CD8+ (15.38%), CTLA4-CD8+ (12.82%), LAG3-CD8+ (33.33%) and PD-1-CD8+ (2.56%) in ALK-positive NSCLC was lower than that in EGFR/KRAS-positive NSCLC. The expression of CD3, CD8 T cells and CD20 B cells was lower in ALK-positive NSCLC than in KRAS-positive NSCLC (p < 0.0001, < 0.005, and < 0.001, respectively). Nevertheless, the level of CD4 helper T cells was higher in ALK-positive NSCLC than in EGFR/KRAS-positive NSCLC (p < 0.0001 and p < 0.05, respectively). The repression of TIM3 was higher in ALK-positive NSCLC than in KRAS-positive NSCLC (p < 0.001). In addition, our data showed that high expression of PD-L1 (HR = 0.177, 95% CI 0.038-0.852, p = 0.027) and CTLA4 (HR = 0.196, 95% CI 0.041-0.947, p = 0.043) was related to lower OS in advanced-stage ALK- rearranged NSCLC patients treated with ALK tyrosine kinase inhibitors (TKIs). Conclusions: Immunosuppressive status was characteristic of the TME in patients with ALK-positive NSCLC compared with EGFR/KRAS-positive NSCLC. High expression of PD-L1 and CTLA4 was an adverse prognostic factor in advanced-stage ALK-rearranged NSCLC patients treated with ALK-TKIs. Immunotherapy for ALK-rearranged patients requires further exploration and validation by clinical trials.
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