The Function of NK Cells in Tumor Metastasis and NK Cell-Based Immunotherapy

Abstract

Metastatic tumors cause the most deaths in cancer patients. Treating metastasis remains the primary goal of current cancer research. Although the immune system prevents and kills the tumor cells, the function of the immune system in metastatic cancer has been unappreciated for decades because tumors are able to develop complex signaling pathways to suppress immune responses, leading them to escape detection and elimination. Studies showed NK cell-based therapies have many advantages and promise for fighting metastatic cancers. We here review the function of the immune system in tumor progression, specifically focusing on the ability of NK cells in antimetastasis, how metastatic tumors escape the NK cell attack, as well as the recent development of effective antimetastatic immunotherapies.

Single-cell allelic transcriptomic analysis unravels intratumoral gene expression heterogeneity linked to TNBC pathogenesis

“…Furthermore, in PT39 and PT84 patients, some genes enriched towards protection from the natural killer (NK) cell-mediated cytotoxicity pathway (Figure 4). Indeed, NK-cell mediated cytotoxicity is important for anti-metastatic activity in cancer and might have a role in tumour heterogeneity (Yu 2023; Topham and Hewitt 2009). Moreover, in PT39 and PT84 we found genes enriching towards ribosome biogenesis pathways; indeed, ribosome biogenesis is crucial for metastasis and therapeutic resistance in cancer (Metge et al 2023; Elhamamsy et al 2022)…”

“…Furthermore, in PT39 and PT84 patients, some genes enriched towards protection from the natural killer (NK) cell-mediated cytotoxicity pathway (Figure 4). Indeed, NK-cell mediated cytotoxicity is important for anti-metastatic activity in cancer and might have a role in tumour heterogeneity (Yu 2023;Topham and Hewitt 2009). Moreover, in PT39 and PT84 we found genes enriching towards ribosome biogenesis pathways; indeed, ribosome biogenesis is crucial for metastasis and therapeutic resistance in cancer (Metge et al 2023;Elhamamsy et al 2022) To further explore the link between allelic expression heterogeneity and TNBC pathogenesis, we wanted to determine the prognostic value of the genes that showed differential allelic expression patterns between the high biallelic and low biallelic cell populations.…”

The killing capacity analysis of tumor infiltrating cytotoxic lymphocytes and impact on lymph node metastasis in differentiated papillary carcinoma of thyroid with BRAF V600E mutation

“…The tumor microenvironment(TME) comprises all the non-cancerous host cells in the tumor and its noncellular components including molecules products [12][13][14]. Among them, cytotoxic lymphocytes were becoming concerned in immune surveillance of cancer and potential immunotherapies, the role of cytotoxic lymphocytes in defending against cancer has been appreciated [15,16].Cytotoxic lymphocytes include natural killer cells and cytotoxic T lymphocytes.NK cells as innate immunity effector cells demonstrate a signi cant role in inhibiting tumor progression [17]. Gogali F et .CD8 + T cells are subpopolation of lymphocytes with the potential to killing tumor cells presenting major histocompatibility complex (MHC) class I molecules [19].Both NK cells and cytotoxic T cells can secrete perforin and granzyme, which play key role in the innate and adapative immune defence line against cancer development [20,21].But studies found tumors had speci c mechanisms to induce tumor immunological tolerance by break immune cell responses [22].An increasing number of studies have found that NK cells and CD8 + T cell dys-function and exhaustion has been verifed in various cancers due to immunosuppression within the TME [23,24],including thyroid cancer [25][26][27].In this study, we investiated the killing capability of NK cells and CTLs to produce perforin and granzyme-B in different regions, including core tumor in ltration region of TME,and marginal in ltration zone of paracancerous tissues.The expression of CD3 + P + ,CD3 + G + ,CD8 + P + ,CD8 + G + CTLs subsets and CD16-CD56 + P + ,CD16-CD56 + G + NK cells subsets were detected by ow cytometry.Our results in this study showed that the percentage of Granzyme-B and perforin were different in TME and paracancerous tissues.…”

Long-term Hematopoietic Transfer of the Anti-Cancer and Lifespan-Extending Capabilities of A Genetically Engineered Blood System by Transplantation of Bone Marrow Mononuclear Cells

“…NK cells are effector lymphocytes of the innate immune system that can rapidly destroy tumor cells and against infectious pathogen 40 . Also, NK cells do not require pre-stimulation for the treatment of cancer cells 41 . Further, the NK lineage could be fully reconstituted 2 weeks after BMT 42 .…”