ArticleCancer immunology, immunotherapy : CII2022
Deciphering the immunosuppressive tumor microenvironment in ALK- and EGFR-positive lung adenocarcinoma.
Article in Cancer immunology, immunotherapy : CII, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 50 citations in OpenAlex.
- Review
- The Treg-cell death axis in lung cancer: implications for immune evasion and novel therapeutic strategies.Molecular cancer · 2026Review
- Molecular Mechanisms and Treatment Strategies of ALK-Positive Lung Cancer: A Beginner's Guide for Patients, Their Families and Carers.Thoracic cancer · 2025Review
- Current Biomarkers in Non-Small Cell Lung Cancer-The Molecular Pathologist's Perspective.Diagnostics (Basel, Switzerland) · 2025Review
- The role of EGFR mutations in sensitivity of PD-1/PD-L1 blockade in non-small cell lung cancer.American journal of cancer research · 2025Review
- New advances in understanding the mechanisms and treatment challenges of ALK-targeted therapy resistance in lung cancer.Cancer drug resistance (Alhambra, Calif.) · 2025Review
- Mechanisms of Resistance to ALK Inhibitors and Corresponding Treatment Strategies in Lung Cancer.International journal of general medicine · 2025Review
- Metal-ion-chelating phenylalanine nanostructures reverse immune dysfunction and sensitize breast tumour to immune checkpoint blockade.Nature nanotechnology · 2024Article
- Unravelling the puzzle of immunotherapeutic efficacy in lung cancer.Translational lung cancer research · 2024Article
- Genomic heterogeneity at baseline is associated with T790M resistance mutations in EGFR-mutated lung cancer treated with the first-/second-generation tyrosine kinase inhibitors.The journal of pathology. Clinical research · 2024Article
- Tackling the challenge of brain involvement in driver-negative non-small cell lung cancer.Translational lung cancer research · 2023Article
- Decoding Oncofusions: Unveiling Mechanisms, Clinical Impact, and Prospects for Personalized Cancer Therapies.Cancers · 2023Review
- High PD-L1 Expression Correlates with an Immunosuppressive Tumour Immune Microenvironment and Worse Prognosis inBiomolecules · 2023Article
- CCR4 Blockade Diminishes Intratumoral Macrophage Recruitment and Augments Survival of Syngeneic Pancreatic Cancer-Bearing Mice.Biomedicines · 2023Article
- Immune Checkpoint Inhibitors Combined with Targeted Therapy: The Recent Advances and Future Potentials.Cancers · 2023Review
- Heterogeneity of tumor immune microenvironment of EGFR/ALK-positive tumors versus EGFR/ALK-negative tumors in resected brain metastases from lung adenocarcinoma.Journal for immunotherapy of cancer · 2023Article
- Can we cure metastaticTranslational cancer research · 2023Article
- Narrative review: immunotherapy in anaplastic lymphoma kinase (ALK)+ lung cancer-current status and future directions.Translational lung cancer research · 2023Review
- CXCR3 predicts the prognosis of endometrial adenocarcinoma.BMC medical genomics · 2023Article
- Changes of tumor microenvironment in non-small cell lung cancer after TKI treatments.Frontiers in immunology · 2023Review
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Authors and funding
23 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionThe advent of immune checkpoint blockade (ICB) has led to significantly improved disease outcome in lung adenocarcinoma (ADC), but response of ALK/EGFR-positive tumors to immune therapy is limited. The underlying immune biology is incompletely understood.
methodsWe performed comparative mRNA expression profiling of 31 ALK-positive, 40 EGFR-positive and 43 ALK/EGFR-negative lung ADC focused on immune gene expression. The presence and levels of tumor infiltration lymphocytes (TILs) as well as fourteen specific immune cell populations were estimated from the gene expression profiles.
resultsWhile total TILs were not lower in ALK-positive and EGFR-positive tumors compared to ALK/EGFR-negative tumors, specific immunosuppressive characteristics were detected in both subgroups: In ALK-positive tumors, regulatory T cells were significantly higher compared to EGFR-positive (fold change: FC = 1.9, p = 0.0013) and ALK/EGFR-negative tumors (FC = 2.1, p = 0.00047). In EGFR-positive tumors, cytotoxic cells were significantly lower compared to ALK-positive (FC = - 1.7, p = 0.016) and to ALK/EGFR-negative tumors (FC = - 2.1, p = 2.0E-05). A total number of 289 genes, 40 part of cytokine-cytokine receptor signaling, were differentially expressed between the three subgroups. Among the latter, five genes were differently expressed in both ALK-positive and EGFR-positive tumors, while twelve genes showed differential expression solely in ALK-positive tumors and eleven genes solely in EGFR-positive tumors.
conclusionTargeted gene expression profiling is a promising tool to read out tumor microenvironment characteristics from routine diagnostic lung cancer biopsies. Significant immune reactivity including specific immunosuppressive characteristics in ALK- and EGFR-positive lung ADC, but not a total absence of immune infiltration supports further clinical evaluation of immune-modulators as partners of ICB in such tumors.
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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.