ULBP1 (UL16 Binding Protein 1)

Its targeting triggers mitochondrial cell death and simultaneously boosts NK cell recognition via ULBP1/NKG2D engagement. TRPM8 targeting in combination with immunotherapy might be, hence, further explored in clinical setting of advanced melanoma.

We summarize current strategies to mitigate immune barriers, discuss practical manufacturing challenges, and analyze available clinical data on NKG2D CAR-T trials. Collectively, these insights underscore both the promise and the hurdles of developing safe, universal, and scalable allogeneic CAR-T therapies for solid malignancies.

Our results provide a possible explanation for the limited synergy between βγ-biased IL-2 and PD-1 blockade: βγ-biased IL-2-activated NK cells eliminate exhausted CD8+ T cells, which are largely tumor-antigen specific T cells, in the TME. These findings underscore the importance of designing next-generation IL-2 variants that, when used in combination with PD-1 inhibitors, minimize NK cell activation to maximize CD8+ T cell anti-tumor responses.

The chemotherapy drug called Adriamycin, often known as doxorubicin (Dox), is used to treat BC, including late stages. ABCG2 mRNA expression is markedly upregulated in MCF7 cells upon P53 and ERK5 downregulation. Collectively, these findings showed that DCA increases the susceptibility of breast cancer cells to Dox through the upregulation of NKG2DL and the downregulation of ABCG2 expression via a p53-ERK5 dependent pathway.

In this article, we reviewed the majority of published NKG2D-based CAR and antibody designs, comparing their respective advantages and disadvantages. We also elaborated how these CARs and antibodies were tested in preclinical cancer models and clinical trials in this review article.

In the AML mouse model, the combination of CUR and ATO exerted a synergistic anti-tumor effect during the progression of AML. In the in vitro KG-1a cell model, it was demonstrated that CUR combined with ATO promoted apoptosis and inhibited proliferation in KG-1a cells through upregulation of the pro-apoptotic protein Caspase3 and downregulation of the anti-apoptotic protein Bcl-2, which was accompanied by a significant increase in autophagosomes in KG-1a cells. In both the co-culture and in vivo models, CUR combined with ATO enhanced the immunotoxic effects of NK cells on KG-1a cells by improving the immunosuppressive microenvironment. The in vivo and in vitro mechanistic studies revealed that CUR combined with ATO primarily upregulated the expression of LC3 protein to promote the formation of autophagosomes in AML cells, downregulated the expression of the hypoxia-inducible factor HIF-1α protein to ameliorate the immunosuppressive microenvironment of AML, and upregulated the expression of MICA protein to activate the NKG2D-NKG2D-L axis. These actions collectively enhanced the immunotoxic and immunosurveillance capabilities of NK cells, thereby inhibiting AML immune evasion. These findings provide novel insights into the mechanisms underlying the synergistic anti-AML effects of CUR combined with ATO and their potential role in inhibiting AML immune evasion.

Importantly, cancer patients with higher levels of FOXM1 and DNMT1, and lower levels of STING and ULBP1, have worse survival and are less responsive to immunotherapy. Collectively, our findings provide key insight into how a tumor-intrinsic transcription factor epigenetically shapes the tumor immune microenvironment, with strong implications for refining existing and designing new cancer immunotherapies.

We also confirmed that SRD5A3 was highly expressed in breast cancer and participated in promoting the proliferation and migration of breast cancer cells. In conclusion, the results of this study provide new insights and strategies for assessing prognosis and implementing precision treatment for breast cancer through the lens of CLMGs.

Enhanced NK cell-mediated cytotoxicity was correlated with expression of NKG2D ligands (P<0.05). In conclusion, sesamin can induce cell cycle arrest and upregulate the expression of NKG2D ligands in MG-63 cells, thereby enhancing NK cell-mediated cytotoxicity against osteosarcoma cells.

In this review, we aim to describe the role of NKG2D and NKG2DLs, and their interactions in the pathogenesis of MS, as well as in other autoimmune diseases such as rheumatoid arthritis (RA), inflammatory bowel disease (IBD), systemic lupus erythematosus (SLE), and celiac disease (CeD). We also assess the potential of these proteins as diagnostic markers and consider future perspectives for targeting NKG2D ligands and their pathways as therapeutic targets in MS.

While NK cells have gained attention for their potent anti-tumour effects without causing graft-versus-host disease (GvHD), thus making them a promising off-the-shelf therapy, our limited understanding of NK killing mechanisms has hindered their clinical application. This study illuminates the crucial role of the activating ligand B7H6 in driving NK cell killing, particularly in the context of LT. Therefore, the expression level of B7H6 could serve as a prognostic marker for patients with LT. Moreover, for the development of NK cell-based immunotherapy, focusing on increasing the level of B7H6 on its cognate receptor, NKp30, could be the most effective strategy.

Overall, the present study demonstrated that ULBP1 was associated with BRCA immunity and might serve as a prognostic and diagnostic biomarker for patients with BRCA. In addition, it might also be a potential target for the immunotherapy of BRCA.