Crosstalk Between NK Cell Receptors and Tumor Membrane Hsp70-Derived Peptide: A Combined Computational and Experimental Study.

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.

Stem cell-based and mesenchymal stem cell derivatives for coronavirus treatment.

Coronavirus disease 2019 (COVID-19) as one of the types of pneumonia was first reported in Wuhan, China in December 2019. COVID-19 is considered the third most common coronavirus among individuals after acute respiratory syndrome (SARS-CoV) and the Middle East respiratory syndrome (MERS-CoV) in the 20th century. Many studies have shown that cell therapy and regenerative medicine approaches have an impressive effect on different dangerous diseases in a way that using a cell-based experiment could be effective for improving humans with severe acute respiratory infections caused by the 2019 novel coronavirus. Accordingly, due to the stunning effects of mesenchymal stem cells (MSCs) and derivatives on the treatment of various diseases, this review focuses on the auxiliary role of MSCs and their derivatives in reducing the inflammatory processes of acute respiratory infections resulted from the 2019 novel coronavirus. The reported MSCs treatment outcomes are significant because these cells prevent the immune system from overactivating and improve, endogenous repair by improving the lung microenvironment after the SARS-CoV-2 infection. The MSCs can be an effective, autologous, and safe treatment, and therefore, share the results. To date, the results of several studies have shown that MSCs and their derivatives can inhibit inflammation. Exosomes act as intercellular communication devices between cells for the transfer of active molecules. In this review, recent MSCs and their derivatives-based clinical trials for the cure of COVID-19 are introduced.