Therapeutic Potential of Natural Killer Cells in Gastric Cancer

Abstract

Gastric cancer (GC) is one of the most common cancers, with a high incidence of cancer death. Despite various therapeutic approaches, the cures and prognosis of advanced GC remain poor. Natural killer (NK) cells, which are known as important lymphocytes in innate immunity, play vital roles in suppressing GC initiation, progression, and metastases. A wide range of clinical settings shows that increasing the number of NK cells or improving NK cell antitumor activity is promising in GC patients. NK cell adoptive therapy (especially expanded NK cells) is a safe and well-tolerated method, which can enhance NK cell cytotoxicity against GC. Meanwhile, cytokines, immunomodulatory drugs, immune checkpoint blockades, antibodies, vaccines, and gene therapy have been found to directly or indirectly activate NK cells to improve their killing activity toward GC. In this review, we summarize recent advancements in the relationship between NK cells and GC and point out all the innovative strategies that can enhance NK cells' function to inhibit the growth of GC.

Flexible ZnO-mAb nanoplatforms for selective peripheral blood mononuclear cell immobilization

“…For example, autologous cell transplantation has been used in clinical settings, including boosting the immune system function for immunotherapy approaches. In particular, the auto-transplantation of ex vivocultivated NK cells has led to an improved outcome in various cancer situations [17][18][19][20] .…”

Progression or suppression: Two sides of the innate lymphoid cells in cancer

“…Additionally, NK cells express two inhibitory immune checkpoint receptors including lymphocyte activation gene 3 and T cell Ig mucin receptor 3 (also known as HAVCR2) . These receptors are under improvement as effective targets when combined with PD1 blockade, showing that NK cells antitumor functions can be revealed via new immunotherapy combinations, while NK cell adoptive therapy showed limited value because of the limited number of available NK cells …”

Natural killer cells in patients with hematologic malignancies, solid tumors and in recipients of hematopoietic stem cell transplantation

“…Several studies have shown the following effects of NK cells in different cancers: NK cells have been shown to be effective in patients with advanced lung cancer; Herceptintreated NK cells have been found to have therapeutic potential in the treatment of patients with human epidermal growth factor receptor 2 (Her2 + ) and Herceptin-intolerant breast cancer; expanded and cryopreserved NK cells are promising candidates for cellular immunotherapy in patients with pancreatic carcinoma; NK cells inhibit metastesis of ovarian carcinoma cells in murine models; CIK cells may become a novel therapeutic modality for rhabdomyosarcoma after allogeneic HSCT; CAR-engineered CIK cells may become valuable in the treatment of HR soft tissue sarcoma in children; and expanded and CIK cells are safe and well tolerated and they enhance cytotoxicity against gastric carcinoma [162,[265][266][267][268][269][270][271]. A meta-analysis, that included 29 clinical trials involving 2610 patients, has been shown that the combination of CIK/DC-CIK immunotherapy and cytotoxic chemotherapy: enhances the immune function of patients, alleviates the adverse effects of chemotherapy, and improves the overall response, disease control, and quality of life [272].…”