ArticleOncoimmunology
Acquisition of tumor cell phenotypic diversity along the EMT spectrum under hypoxic pressure: Consequences on susceptibility to cell-mediated cytotoxicity.
Article in Oncoimmunology. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 79 citations in OpenAlex.
- Targeting Aggressive Prostate Carcinoma Cells with Mesothelin-CAR-T Cells.Biomedicines · 2025Article
- ELK3-CYFIP2 axis-mediated actin remodeling modulates metastasis and natural killer cell responses in triple-negative breast cancer.Journal of experimental & clinical cancer research : CR · 2025Article
- Differentially expressed growth factors and cytokines drive phenotypic changes in transmissible cancers.Discovery immunology · 2025Article
- The molecular features of lung cancer stem cells in dedifferentiation process-driven epigenetic alterations.The Journal of biological chemistry · 2024Review
- The activity of tertiary lymphoid structures in high grade serous ovarian cancer is governed by site, stroma, and cellular interactions.Cancer cell · 2024Article
- Spatial transcriptomic analysis of primary and metastatic pancreatic cancers highlights tumor microenvironmental heterogeneity.Nature genetics · 2024Article
- Grainyhead-like-2, an epithelial master programmer, promotes interferon induction and suppresses breast cancer recurrence.Molecular immunology · 2024Article
- Epithelial-to-mesenchymal transition in cancer progression: unraveling the immunosuppressive module driving therapy resistance.Cancer metastasis reviews · 2024Review
- Immunosurveillance encounters cancer metabolism.EMBO reports · 2024Review
- Advancing immunotherapy for melanoma: the critical role of single-cell analysis in identifying predictive biomarkers.Frontiers in immunology · 2024Review
- Tumour response to hypoxia: understanding the hypoxic tumour microenvironment to improve treatment outcome in solid tumours.Frontiers in oncology · 2024Review
- EMT-induced immune evasion: connecting the dots from mechanisms to therapy.Clinical and experimental medicine · 2023Review
- Harnessing epithelial-mesenchymal plasticity to boost cancer immunotherapy.Cellular & molecular immunology · 2023Review
- Effect of tumor microenvironment on ferroptosis: inhibition or promotion.Frontiers in oncology · 2023Review
- Epithelial-Mesenchymal Plasticity in Tumor Immune Evasion.Cancer research · 2022Review
- Slug and Vimentin downregulation at the metastatic site is associated with Skip-N2 metastasis of lung adenocarcinoma.Discover oncology · 2022Article
- Prognostic Modeling of Lung Adenocarcinoma Based on Hypoxia and Ferroptosis-Related Genes.Journal of oncology · 2022Article
- Mechanism underlying the immune checkpoint inhibitor-induced hyper-progressive state of cancer.Cancer drug resistance (Alhambra, Calif.) · 2022Review
- The Effect of Hypoxia and Hypoxia-Associated Pathways in the Regulation of Antitumor Response: Friends or Foes?Frontiers in immunology · 2022Review
- Infiltrating T-cell abundance combined with EMT-related gene expression as a prognostic factor of colon cancer.Bioengineered · 2021Article
Corrections and comments
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Authors and funding
9 authors at 7 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tumor escape to immunosurveillance and resistance to immune attacks present a major hurdle in cancer therapy, especially in the current era of new cancer immunotherapies. We report here that hypoxia, a hallmark of most solid tumors, orchestrates carcinoma cell heterogeneity through the induction of phenotypic diversity and the acquisition of distinct epithelial-mesenchymal transition (EMT) states. Using lung adenocarcinoma cells derived from a non-metastatic patient, we demonstrated that hypoxic stress induced phenotypic diversity along the EMT spectrum, with induction of EMT transcription factors (EMT-TFs) SNAI1, SNAI2, TWIST1, and ZEB2 in a hypoxia-inducible factor-1α (HIF1A)-dependent or -independent manner. Analysis of hypoxia-exposed tumor subclones, with pronounced epithelial or mesenchymal phenotypes, revealed that mesenchymal subclones exhibited an increased propensity to resist cytotoxic T lymphocytes (CTL), and natural killer (NK) cell-mediated lysis by a mechanism involving defective immune synapse signaling. Additionally, targeting EMT-TFs, or inhibition of TGF-β signaling, attenuated mesenchymal subclone susceptibility to immune attack. Together, these findings uncover hypoxia-induced EMT and heterogeneity as a novel driving escape mechanism to lymphocyte-mediated cytotoxicity, with the potential to provide new therapeutic opportunities for cancer patients.
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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.