ArticleFrontiers in immunology2015
Correlation of Hsp70 Serum Levels with Gross Tumor Volume and Composition of Lymphocyte Subpopulations in Patients with Squamous Cell and Adeno Non-Small Cell Lung Cancer.
Article in Frontiers in immunology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 81 citations in OpenAlex.
- Radiochemotherapy combined with NK cell transfer followed by second-line PD-1 inhibition in a patient with NSCLC stage IIIb inducing long-term tumor control: a case study.Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al] · 2019Trial
- Exogenous Heat Shock Proteins in Oncology: Biological Roles and Clinical Implications.Cancers · 2026Review
- Circulating Hsp70 Reflects Tumor Burden and Stage-Dependent Disease Progression Across Multiple Solid Tumor Entities.Cancers · 2026Article
- Fluorescence Immunosensor with Phage Antibodies for Heat Shock Protein 70 Detection.Biosensors · 2026Article
- Density and maturity ratio of tertiary lymphoid structures in stage II-III non-small cell lung cancer predict postoperative recurrence risk.Translational lung cancer research · 2025Article
- Circulating Hsp70: a tumor biomarker for lymph node metastases and early relapse in thoracic cancer.BMC cancer · 2025Article
- Improved ex vivo fluorescence imaging of human head and neck cancer using the peptide tracer TPP-IRDye800 targeting membrane-bound Hsp70 on tumor cells.British journal of cancer · 2024Article
- Extracellular Hsp70 and Circulating Endometriotic Cells as Novel Biomarkers for Endometriosis.International journal of molecular sciences · 2024Article
- Diversity of extracellular HSP70 in cancer: advancing from a molecular biomarker to a novel therapeutic target.Frontiers in oncology · 2024Review
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- Clinical implications of heat shock protein 70 in oral carcinogenesis and prediction of progression and recurrence in oral squamous cell carcinoma patients: a retrospective clinicopathological study.European journal of medical research · 2023Article
- Hsp70-A Universal Biomarker for Predicting Therapeutic Failure in Human Female Cancers and a Target for CTC Isolation in Advanced Cancers.Biomedicines · 2023Article
- The Role of Extracellular Heat Shock Proteins in Cardiovascular Diseases.Biomedicines · 2023Review
- Circulating Hsp70 Levels and the Immunophenotype of Peripheral Blood Lymphocytes as Potential Biomarkers for Advanced Lung Cancer and Therapy Failure after Surgery.Biomolecules · 2023Article
- Roles of tissue-resident immune cells in immunotherapy of non-small cell lung cancer.Frontiers in immunology · 2023Review
- Protocol of the HISTOTHERM study: assessing the response to hyperthermia and hypofractionated radiotherapy in recurrent breast cancer.Frontiers in oncology · 2023Article
- Immunohistochemical, Flow Cytometric, and ELISA-Based Analyses of Intracellular, Membrane-Expressed, and Extracellular Hsp70 as Cancer Biomarkers.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Elevated circulating Hsp70 levels are correlative for malignancies in different mammalian species.Cell stress & chaperones · 2023Article
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Heat-shock protein 70 (Hsp70) is frequently found on the plasma membrane of a large number of malignant tumors including non-small cell lung cancer (NSCLC) and gets released into the blood circulation in lipid vesicles. On the one hand, a membrane (m)Hsp70-positive phenotype correlates with a high aggressiveness of the tumor; on the other hand, mHsp70 serves as a target for natural killer (NK) cells that had been pre-stimulated with Hsp70-peptide TKD plus low-dose interleukin-2 (TKD/IL-2). Following activation, NK cells show an up-regulated expression of activatory C-type lectin receptors, such as CD94/NKG2C, NKG2D, and natural cytotoxicity receptors (NCRs; NKp44, NKp46, and NKp30) and thereby gain the capacity to kill mHsp70-positive tumor cells. With respect to these results, the efficacy of ex vivo TKD/IL-2 stimulated, autologous NK cells is currently tested in a proof-of-concept phase II clinical trial in patients with squamous cell NSCLC after radiochemotherapy (RCT) at the TUM. Inclusion criteria are histological proven, non-resectable NSCLC in stage IIIA/IIIB, clinical responses to RCT and a mHsp70-positive tumor phenotype. The mHsp70 status is determined in the serum of patients using the lipHsp70 ELISA test, which enables the quantification of liposomal and free Hsp70. Squamous cell and adeno NSCLC patients had significantly higher serum Hsp70 levels than healthy controls. A significant correlation of serum Hsp70 levels with the gross tumor volume was shown for adeno and squamous cell NSCLC. However, significantly elevated ratios of activated CD69(+)/CD94(+) NK cells that are associated with low serum Hsp70 levels were observed only in patients with squamous cell lung cancer. These data might provide a first hint that squamous cell NSCLC is more immunogenic than adeno NSCLC.
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