ArticleeLife2022
Transient cell-in-cell formation underlies tumor relapse and resistance to immunotherapy.
Article in eLife, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 2 of them syntheses that pooled it.
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Who cites it
38 citing papers in PubMed, 2 syntheses or guidelines pooled it, 52 citations in OpenAlex.
- A bibliometric and visualization analysis of entosis research from 2007 to 2024.Frontiers in oncology · 2024Pooled it
- Pooled it
- Comprehensive machine learning identifies anoikis signatures predicting therapeutic resistance and survival in gastric cancer.Scientific reports · 2026Article
- Exosomal circRNAs in hepatocellular carcinoma: Implications for the development and therapeutic resistance of hepatocellular carcinoma (Review).International journal of oncology · 2026Review
- A comprehensive analysis identified BECN1 as potential diagnostic biomarker for homotypic cell-in-cell in non-small cell lung cancer through integrated bioinformatics and clinical validation approaches.Discover oncology · 2026Article
- Mechanisms and therapeutic strategies for immunotherapy resistance in gastric cancer.Cancer cell international · 2025Review
- Cell-in-Cell Structures in Colorectal Cancer: A Proposed Assessment Method and Correlation with Established Poor Prognostic Factors.Journal of personalized medicine · 2025Article
- Shelter in place: live CLL cells inside the bone marrow fibroblasts and its implication in residual disease persistence.Blood neoplasia · 2025Article
- Molecular Dynamics of Trogocytosis and Other Contact-Dependent Cell Trafficking Mechanisms in Tumor Pathogenesis.Cancers · 2025Review
- Dual role of interferon-gamma in the response of melanoma patients to immunotherapy with immune checkpoint inhibitors.Molecular cancer · 2025Review
- LncRNA MIR31HG facilitates immune escape in head and neck squamous cell carcinoma by promoting heterotypic cell-in-cell formation.American journal of cancer research · 2025Article
- Case Report: Comparison different response after neoadjuvant chemotherapy of the breast with cell-in-cell-report of two cases.Frontiers in medicine · 2025Article
- Cell-in-cell associated lncRNA signature predicts prognosis and immunotherapy response in gastric cancer.Frontiers in oncology · 2025Article
- Colorectal cancer stem cells develop NK cell resistance via homotypic cell-in-cell structures suppressed by Stathmin1.Theranostics · 2025Article
- Establishment and clinical value of a circulating tumor cell system based on a multi-site immune lipid magnetic sphere technique in laryngopharyngeal head and neck tumors.American journal of cancer research · 2025Article
- Cell hiding in colorectal cancer: correlation with response to chemotherapy in vitro and in vivo.Scientific reports · 2024Article
- Co-delivery of siRNA and cisplatin via electrospun Nanofibrous membranes for synergistic treatment of malignant melanoma.Heliyon · 2024Article
- Adaptations of membrane trafficking in cancer and tumorigenesis.Journal of cell science · 2024Review
- Entosis: the core mechanism and crosstalk with other cell death programs.Experimental & molecular medicine · 2024Article
- Perspective view of allogeneic IgG tumor immunotherapy.Cancer cell international · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
23 authors at 6 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Despite the remarkable successes of cancer immunotherapies, the majority of patients will experience only partial response followed by relapse of resistant tumors. While treatment resistance has frequently been attributed to clonal selection and immunoediting, comparisons of paired primary and relapsed tumors in melanoma and breast cancers indicate that they share the majority of clones. Here, we demonstrate in both mouse models and clinical human samples that tumor cells evade immunotherapy by generating unique transient cell-in-cell structures, which are resistant to killing by T cells and chemotherapies. While the outer cells in this cell-in-cell formation are often killed by reactive T cells, the inner cells remain intact and disseminate into single tumor cells once T cells are no longer present. This formation is mediated predominantly by IFNγ-activated T cells, which subsequently induce phosphorylation of the transcription factors signal transducer and activator of transcription 3 (STAT3) and early growth response-1 (EGR-1) in tumor cells. Indeed, inhibiting these factors prior to immunotherapy significantly improves its therapeutic efficacy. Overall, this work highlights a currently insurmountable limitation of immunotherapy and reveals a previously unknown resistance mechanism which enables tumor cells to survive immune-mediated killing without altering their immunogenicity.
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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.