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Hepatocellular carcinoma (HCC) is one of the most common lethal cancers worldwide. Natural killer cells (NK cells) play a key role in liver immunosurveillance, but in the tumor microenvironment, NK cells are readily depleted, as evidenced by down-regulation of activating receptors, reduced cytokine secretion, and attenuated killing function. The up-regulation of inhibitory receptors, such as PD-1, TIM-3, and LAG-3, further exacerbates the depletion of NK cells. Combined blockade strategies targeting these immunosuppressive mechanisms, such as the combination of PD-1 inhibitors with other inhibitory pathways (eg. TIM-3 and LAG-3), have shown potential to reverse NK cell exhaustion in preclinical studies. This article explores the promise of these innovative strategies in HCC immunotherapy, providing new therapeutic directions for optimizing NK cell function and improving drug sensitivity.
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http://dx.doi.org/10.3389/fonc.2024.1502270 | DOI Listing |
Mol Immunol
September 2025
Department of Surgical Urology, the Third Affiliated Hospital of Soochow University, No. 185, Jiuqian Street, Changzhou, Jiangsu 213003, China. Electronic address:
The confirmed tumor-inhibitory effects of the 30 kDa Momordica anti-human immunodeficiency virus protein (MAP30) have yet to be complemented by an exploration into its mechanism of action on tumor development and metastasis. For this purpose, we delved into the intrinsic mechanism of MAP30 in bladder cancer (BC). Here, we demonstrated that MAP30 markedly suppressed the proliferation, migration, invasion, and angiogenic capabilities of human BC cells in vitro, and the tumor metastatic potential in vivo.
View Article and Find Full Text PDFInt J Biol Macromol
September 2025
Department of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, 213003, China; Jiangsu Engineering Research Center for Tumor Immunotherapy, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, 213003, China; Institute of Cell The
Despite its potential as a cancer immunotherapy, wild-type IL-2 is limited by dose-limiting toxicities, including vascular leak syndrome, and its strong activation of regulatory T cells (Tregs), which dampens anti-tumor immunity. These drawbacks are largely driven by IL-2's binding to IL-2Rα, and avoiding this interaction can reduce IL-2-associated toxicities, although it cannot completely eliminate them. To overcome these limitations, βγ-biased IL-2 variants (Non-α-IL-2) have been developed to selectively activate effector T and NK cells.
View Article and Find Full Text PDFJ Biol Chem
September 2025
State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, China; Hubei Hongshan Laboratory, Wuhan, Hubei, 430070, China. Electronic address:
Ferroptosis is a novel type of programmed cell death caused by iron-dependent lipid peroxidation. Targeted induction of ferroptosis holds great promise for cancer treatment. SNHG, a newly recognized lncRNA family, has been reported to implicate in the proliferation, invasion, migration or drug resistance of cancer cells.
View Article and Find Full Text PDFCancer Lett
September 2025
Department of Cell, Development and Cancer Biology, Knight Cancer Institute, Oregon Health and Sciences University, Portland, OR, USA; Brenden-Colson Center for Pancreatic Care, Oregon Health and Science University, Portland, OR, USA.
Gemcitabine, a ribonucleotide reductase (RNR) inhibitor, is active in pancreatic ductal carcinoma (PDAC) patients, but unfortunately has a limited impact on long term outcomes. Gemcitabine induces nucleotide deficiency, DNA damage including single stranded DNA (ssDNA) and replication stress (RS). DNA damage can activate cyclic GMP-AMP synthase (cGAS), leading to genome instability, micronucleus generation, and immune activation.
View Article and Find Full Text PDFEur J Pharmacol
September 2025
Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China. Electronic address:
Background: Immunotherapy (IO) combined with tyrosine kinase inhibitors (TKI) are now first-line therapy for advanced renal cell carcinoma (RCC), though reliable predictive biomarkers remain elusive. Recent evidence demonstrates that karyopherin α2 subunit (KPNA2), a nuclear transport regulator, plays key roles in tumorigenesis and therapy resistance.
Methods: Two cohorts were analyzed: an institutional cohort of metastatic RCC patients (ZS-MRCC) and the phase III JAVELIN Renal 101 trial cohort.