MICA (MHC Class I Polypeptide-Related Sequence A)

Recombinant protein assays and in silico analyses support direct interaction between CRT and non-glycosylated MICA, but not with fully glycosylated eukaryotic MICA. These findings identify CRT-dependent retention of MICA as a physiological checkpoint that may be dysregulated in melanoma to promote immune evasion.

We review the effects of MICA amino acid polymorphism on the affinity of the NKG2D signal pathway and analyze in detail the specific role of MICA amino acid polymorphism in tumor immunity. The study provides a reference for understanding the mechanism of anti-tumor immune response by NK cells or other immune cells, as well as a theoretical basis for considering the MICA-NKG2D signal axis for anti-tumor immune therapy in future clinical practice.

Their downregulation attenuates NK cell function, promoting cervical cancer cell proliferation and survival via the Toll signaling pathway. These findings highlight the potential of targeting MICA/B-NK cell interactions as a therapeutic strategy for cervical cancer.

Conversely, the MICA-129 homozygous allele A/A (Met/Met) variant was related to more advanced clinical characteristics, such as increased tumor invasion depth (T3/4; P = .0261, OR = 2.10), driver gene mutation (P = .0363, OR = 2.65), and KRAS mutation (P = .0392, OR = 2.23). Additionally, patients with carbohydrate antigen 19-9-positive CRC had a lower MICA-129 Met/Val variation, whereas those with carcinoembryonic antigen-positive CRC had a higher MICA-129 Met/Met variant (P = .0330/OR = 0.22 and P = .0034/OR = 2.99, respectively).

In vivo studies using an NSG mouse model demonstrate robust activation of patient-derived T and NK cells, leading to potent anti-MM effects. This work presents a dual-pronged immunotherapeutic strategy to overcome immune suppression in MM, offering a synergistic approach to harness both adaptive and innate immunity for enhanced cancer immunotherapy.

These results highlight MICA as a novel biomarker for malignancy risk in DM, providing potential clinical utility for identifying patients at high risk. Key Points • This study demonstrates a significant causal association between elevated plasma MICA protein levels and an increased risk of developing dermatomyositis using proteome-wide Mendelian randomization. • ELISA-based validation in a clinical cohort confirms that serum MICA levels were significantly elevated in patients with DM/CADM, especially those with malignancy, supporting its role as a malignancy biomarker.

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.

CYAD-02 presented an higher engraftment and an improved clinical activity (17% objective response rate) compared to CYAD-01 (no objective response). Altogether, our data provide proof of principle that knock-down of MICA/B can enhance CAR T-cell persistence and efficacy while maintaining a good safety profile.

Mechanistically, CKS2 activated the PI3K/AKT signaling, reduced major histocompatibility complex (MHC) class I chain-related protein A (MICA) expression, and inhibited NKT cell activity, resulting in immune escape, which was effectively mitigated by PI3K inhibitors. The findings suggest that CKS2 can serve as a valuable biomarker and an effective target for the prevention and screening of uterine sarcoma and can modify the antitumor immune response in uterine sarcoma.

Mechanistically, mbIL2 mitigated activation-induced apoptosis and suppressed exhaustion during tumor engagement, thereby sustaining NK cell viability. These findings establish mbIL2 as a critical enhancer of CAR-NK cell persistence and antitumor function, offering a clinically translatable strategy to overcome the limitations of cytokine-dependent therapies.

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.

Solasonine inhibits gastric cancer progression and restores sensitivity of gastric cancer to NK cells through inducing DNA demethylation of the MICA promoter in vitro and in vivo. This study provides application prospects for solasonine anti-tumor therapy.