Crosstalk Between NK Cell Receptors and Tumor Membrane Hsp70‐Derived Peptide: A Combined Computational and Experimental Study
Source abstract
Abstract
Abstract Natural killer (NK) cells are central components of the innate immunity system against cancers. Since tumor cells have evolved a series of mechanisms to escape from NK cells, developing methods for increasing the NK cell antitumor activity is of utmost importance. It is previously shown that an ex vivo stimulation of patient‐derived NK cells with interleukin (IL)‐2 and Hsp70‐derived peptide TKD (TKDNNLLGRFELSG, aa450‐461) results in a significant upregulation of activating receptors including CD94 and CD69 which triggers exhausted NK cells to target and kill malignant solid tumors expressing membrane Hsp70 (mHsp70). Considering that TKD binding to an activating receptor is the initial step in the cytolytic signaling cascade of NK cells, herein this interaction is studied by molecular docking and molecular dynamics simulation computational modeling. The in silico results showed a crucial role of the heterodimeric receptor CD94/NKG2A and CD94/NKG2C in the TKD interaction with NK cells. Antibody blocking and CRISPR/Cas9–mediated knockout studies verified the key function of CD94 in the TKD stimulation and activation of NK cells which is characterized by an increased cytotoxic capacity against mHsp70 positive tumor cells via enhanced production and release of lytic granules and pro‐inflammatory cytokines.
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Research context
OpenAlex topics: Immune Cell Function and Interaction · Heat shock proteins research · T-cell and B-cell Immunology
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
Pharmaceutical Biotechnology Department of Pharmacy Ludwig‐Maximilians‐Universität (LMU) 81377 Munich Germany
Heinz‐Nixdorf‐Chair of Biomedical Electronics Campus Klinikum München rechts der Isar TranslaTUM Technische Universität München 81675 Munich Germany
Department of Biology Faculty of Science Shahid Chamran University of Ahvaz Ahvaz 6135783151 Iran
Behbahan Faculty of Medical Sciences Behbahan 6361796819 Iran
Institute of Molecular Oncology and Functional Genomics School of Medicine Technische Universität München 81675 Munich Germany
Central Institute for Translational Cancer Research (TranslaTUM) School of Medicine Technische Universität München 81675 Munich Germany
Department of Pathobiology Faculty of Veterinary Medicine Shahid Chamran University of Ahvaz Ahvaz 6135783151 Iran
Department of Radiation Oncology School of Medicine Technische Universität München 81675 Munich Germany
Department of Otorhinolaryngology School of Medicine Technische Universität München 81675 Munich Germany
John van Geest Cancer Research Centre School of Science and Technology Nottingham Trent University Nottingham NG11 8NS UK
Funding
Deutsche Forschungsgemeinschaft
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