FASLG (Fas ligand)

Using global sensitivity analysis, we also found that GSK3B, which is responsible for the deactivation of the NFAT, is also predicted to further increase T cell activation when knocked out. In addition, we predict that PDCD1, FAS and CTLA4 can be knocked-out in combination with CISH to further enhance T cell activation and prevent exhaustion and apoptosis.

Gene expression analysis showed upregulation of FAS (1.67-fold; P<0.001), FASL (1.28 fold; P=0.005), BAX (2.34 fold; P<0.001), BAK (1.29 fold; P=0.004), and BIM (1.4 fold; P<0.001) and downregulation of BCL-2 (0.44 fold; P<0.001), BCL-XL (0.47 fold; P<0.001), PI3K (P<0.001), AKT (P<0.001), and MTOR (P<0.001). Vipera raddei kurdistanica venom may exert selective cytotoxic effects against gastric cancer cells and may induce apoptosis through both intrinsic and extrinsic pathways, potentially via inhibition of the PI3K/AKT/mTOR signalling axis.

Importantly, pro-inflammatory cytokines such as IL-6, IL-10, and IFN-γ remained at low levels, suggesting a favorable safety profile. These findings support the therapeutic potential of CD138-targeted BATs as a promising and potentially safer cellular immunotherapy for the treatment of MM.

The combined data indicate that ErbB2, perhaps by driving micronuclei formation, has immunogenic properties that manifest in the form of increased T-cell infiltration and expansion, which can be exploited therapeutically by combining PD1-directed checkpoint blockade with ErbB2-targeted therapy.

However, the interaction between CMTM6 and FAS is absent in human cells due to the difference in three amino acids at the boundary of the FAS extracellular and transmembrane domains. Altogether, our findings urge caution when translating promising data regarding the targeting of CMTM6 from mouse cancer models to potential human therapies.

Patients received radiotherapy (50.4 Gy/28 in fractions on 5 days per week), concurrent chemotherapy (paclitaxel 135 mg/m2 d1+ cisplatin 25 mg/m2 d1-3, q3w, 2 cycles), and QL1706 (5 mg/kg q3w for up to 1 year [total of 18 cycles]). QL1706 combined with chemoradiotherapy demonstrated potential antitumor activity and manageable toxicity, supporting further investigation. National Natural Science Foundation of China, State Key Laboratory of Druggability Evaluation and Systematic Translational Medicine, Tianjin Key Medical Discipline Construction Project, and Tianjin Key Medical Discipline (Specialty) Construction Project.

We targeted T and NK92 ACDVs to cancer cells possessing the xenoantigen, N-glycolyl neuraminic acid GM3 ganglioside, using the 14f7hT antibody or the tumour antigen, epidermal growth factor receptor, using the nimotuzumab antibody...14F7hT-conjugated NK92 ACDVs showed cytotoxic activity against chronic lymphocytic leukaemia biopsies. This research shows the potential for using antibody-conjugated, cytotoxic T and NK ACDVs as a feasible and effective approach for tumour-targeted immunotherapy.

Collectively, these findings demonstrate that the immunomodulatory effects of MSCs on breast cancer are highly dependent on the timing of their administration. Mesenchymal stem cells delivered during early tumor development enhance phenotypes consistent with antitumor potential and suppress tumor progression, whereas administration during later stages promotes immune evasion and tumor growth.

ObjectivesThis retrospective study presents an integrative transcriptomic approach for recurrent and/or metastatic head and neck squamous cell carcinoma (R/M HNSCC) by developing an immune response predictive score (IORPS) derived from tumor microenvironment (TME) transcriptomic profiles.MethodsA total of 30 R/M HNSCC patients treated with pembrolizumab or nivolumab, with available immune TME profiling data, were analyzed. The clinical relevance of IORPS was further validated using two external cohorts from the GEO database (CLB-IHN: GSE159067 and GHPS: GSE159141).ResultsBy comparing immune tumor microenvironment (TME) profiles between good and poor responders, GZMH, IFNG, and FASLG were identified as key DEGs with significantly higher expression in favorable immunotherapy responders. The IORPS, derived from transcriptomic profiling, demonstrated robust predictive accuracy for both immunotherapy response and survival outcomes in patients with R/M HNSCC.ConclusionCompared with the variable predictive performance of current biomarkers such as TPS and CPS, IORPS provides improved accuracy and reliability in identifying and stratifying patients most likely to benefit from immune checkpoint blockade therapy.

The findings, while insightful, require validation in larger cohorts. Future research should integrate molecular profiling and functional assays to clarify the underlying mechanisms.

Although several DNA repair gene polymorphisms have been explored, findings remain inconsistent and limited by populations and SNPs studied. Larger, well-designed studies with standardized methodologies are needed to confirm these associations and identify genetic markers for predicting high-risk patients for CIO.

These findings suggest that serum levels of sFas and sFasL could be useful tumor markers with prognostic value in pancreatic adenocarcinomas. Increased sFas secretion may reflect a mechanism for apoptotic escape of cancer cells.