Nature sub-magazine reviews in-depth interpretation! NK cell-mediated immune editing mechanism for cancer metastasis!

, June 29, 2020
/PRNewswire/ -- In a review published in the international journal nature cancer, scientists from the QiMR Berghofer Medical Institute in Australia discussed the co-brokered by NK cells in a review published in the international journal nature cancerImmune editing mechanism of cancer metastasis, natural killer cells (NK cells) play a key role in controlling disease metastasis, and studies have shown that NK cells can prioritize the control of single-clone metastasis from single circulatingtumorscells, rather than multi-clone transfer derived from cell clusters, and the results further demonstrate that NK cells or immuno-editing of metastatic cells are relatedDespite recent advances in cancer treatment, cancer metastasis remains the leading cause of death in solid cancer patients such asbreast cancer, and cancer metastasis is a multi-step process that includes tumor attack, internal circulation of blood circulation, substantial externality of the far end organ and progress from micro-transfer; Circulating tumor cells (CTCs) survive the metastasis process and can initiate metastatic lesions; NK cells are identified by key congenital immune cells that control metastasis, and NK cell-mediated immune pressures may also be predicted to have an effect on the fate of CTCs; just as Darwin's selective pressureis are thought to shape the tumor's phenotypes and genotypes, a process known as "the editing of cancer"(cancered, " the researchers say, NK cells can selectively control a single CTC-derived monoclonal metastasis, but not CTC cluster-derived multi-clone metastasis, which may provide researchers with new ideas to reveal NK cell-mediated metastasisimmune editing of tumorcellsPhoto Credit: Nakamura, K., et alNat Cancerdoi:10.1038/s43018-020-0081-z
To understand the different susceptibility of individual CTCs and CTCs clusters to immune system-mediated elimination, the researchers used an experimental model already established to distinguish between monoclonal transfer and multi-clone transfer; Green) and mCherry (red) fluorescent labeled breast cancer cells in mice, and the GFP-positive cells and mCherry-positive cells were injected into the mice according to a 1:1 mixture, followed by an assessment of lung metastasis of cancer cells, the mixed-color lung metastasis reflected the multi-clone source from CTC clusters, whereas a single CTCs also produced monochrome, monoclonal metastasis The researchers found that up to 50% of metastatic lesions in mice with the same immune activity were multi-clone, however, surprisingly, when the researchers repeated the same experiment in immunodeficiency mice that lacked mature lymphocytes, the frequency of monochromatic monoclonal metastasis increased significantly to 80% of the metastatic lesions %, it is worth noting that in immunodeficiency mouse organisms, the absence of antibody-mediated NK cells will also increase the incidence of monoclonal metastasis, while NK cell over-passing to immunodeficiency mice will significantly reduce the transfer of monoclonal, the relevant results show that NK cells will give priority to control single-CTC-derived monoclonal transfer epithelial hypertheract conversion (EMT) is a key process in the migration and invasive properties of epithelial tumor cells, usually, a single CTCs have interstitial properties, in contrast, the collective diffusion of larger mucus tumor cells will lead to the production of clusters of CTC, so CTC clusters also contain tumor cells that retain epithelial characteristics The researchers speculated that the phenotype of interstitial vs epithelial CTC may be the reason for its elimination of sensitivity to NK cell mediate, in order to solve this problem, the researchers used eight types of breast cancer cell lines with epithelial cell properties or interstitial cell characteristics for NK cell co-culture experiments, in fact, NK cells with interstitial characteristics of non-cluster cell lines show strong cell toxicity, and cells with epithelial characteristics of cells tend to have a certain degree of resistance to NK-mediated cells the researchers then analyzed the mechanism of differences in the sensitivity of NK cell-mediated cytotoxicity, where the active performance of NK cells was regulated by the balance between the activation receptor signal and the inhibitory receptor signal, while The NKG2D (Natural Killer-Receptor Group 2, natural killer-receptor group 2, Member D) is a key active receptor that identifies pressure-induced automatiosis on malignant lyte cells, while NK cell inhibitors identify their main tissue compatibility class 1 complex to protect normal cells from cytotoxicity mediated by NK cells Using cytokine TGF-beta to stimulate the EMT process and induce miR-200c to inhibit EMT, the researchers found that multiple NKG2Ds in tumor cells carrying interstitial phenotypes showed high expression, while the expression of the main tissue compatibility class 1 complex The level is lower, which may help explain why interstitial tumors are more susceptible to cytotoxicity than those mediated by NK cells, and in fact, the growth level of metastatic tumors in the body is lower than that of miR-200c-induced epithelial tumors It is worth noting that the culling of NK cells or the blockofing of NKG2D will also increase the metastatic tumor load of interstitial tumors to a lesser extent, which may support the hypothesis that NKG2D-dependent NK cytotoxicity plays a key
role in controlling interstitial-charged tumors review article, the researchers explained the survival advantages of CTC clusters under the immune supervision of NK cell-mediated, however, the following may also be closely related to the sensitivity and resistance of NK cell-mediated metastasis control, first of all, the EMT process is a highly malleable process, and CTCs capable of reaching distant end organs may escape THE monitoring of NK cells by reversely intheptop conversion process, and further research between NK cells and epithelial remodeling of tumor cells Second, immunosuppressive metastasis habitat may also promote tumor cells to escape THE elimination of NK cell-mediated, in particular, researchers do not currently know the mechanism to control the balance between immune system-mediated sleep and metastatic growth, and third, there is research evidence that pilot cells with interstitial properties play a key role in the collective migration and propagation of CTC clusters, and it is possible that the elimination of NK cell-mediated pilot cells can improve the metastatic potential of CTC clusters Because CTC clusters can be the leading cause of cancer metastasis, researchers need to better understand the biological characteristics of CTC clusters to provide more clues to the development of therapeutic interventions, especially in the early stages of the establishment and progression of distant metastasis lesions, and finally, although CTC clusters demonstrate greater resistance to the natural immune supervision mediated by NK cells, researchers are still very interested in the study of whether it is intended to be designed Increasing the immunotherapeutic methods of NK cells (such as NK cell checkpoint molecular blocking) can improve the control of cancer metastasis
; (BioValleyBioon.com) References: Nakamura, K., Smyth, M.J Immunoediting of cancer metastasis by NK cells
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Nat Cancer (2020) doi: 10.1038/s43018-020-0081-z
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