TMB-L

Importantly, knockdown of IGF2BP1 along with anti-GD2 immunotherapy induced a synergistic immunogenic effect and achieved a potent antitumor response in an HR-NB mouse model, with increased accumulation of effector CD8+ T cells and CD86+  macrophages but decreased MDSC numbers in the tumor microenvironment. Thus, disrupting NB cancer cell IGF2BP1-mediated immunosuppression is a potential approach for improving the efficacy of anti-GD2 immunotherapy towards HR-NBs.

This case highlights that a definitive distinction between WDPMT and malignant mesothelioma is paramount, as it dictates a radically different management strategy. Integration of immunohistochemistry (particularly BAP1) and molecular profiling is essential for accurate diagnosis and can prevent overtreatment. For appropriately selected patients with WDPMT, conservative management with active surveillance represents a safe and effective approach, underscoring the value of precision medicine in guiding patient-centric care.

While the biological and molecular determinants underlying the response rates observed in the NICHE-2 trial remain to be fully elucidated, the work by Tan et al. suggests that biomarker-guided neoadjuvant immunotherapy could represent a valuable strategy to achieve pathological responses in early-stage pMMR CC, despite its clinical relevance requiring further evaluation.

SULmax is an independent predictor of both PD-L1-Pos and TMB-High in ADC. The clinical-SULmax combined models effectively predicted PD-L1-Pos and TMB-High status, as well as PD-L1-Neg and TMB-Low status in ADC, indicating the clinical utility in patient selection and immunotherapy response stratification.

Transcriptome cluster comparative analysis placed its expression profile close to pancreas neuroendocrine tumors. This case suggests NR4A2 as a functionally substitute for NR4A3 in tumorigenesis and a neuroendocrine lineage differentiation for a subset of EMC.

In the absence of specific FANCJ-targeting compounds, we evaluated the phenotypic and molecular effects of pharmacological inhibition of the MUS81 endonuclease, which functions downstream of FANCJ in restarting stalled replication forks. When combined with CHK1 inhibition, we observed synergistic effects on neuroblastoma cell growth and survival, supporting further development of on-target MUS81 inhibitors for in vivo preclinical testing and future clinical trials aimed at overcoming replication stress resistance in high-risk neuroblastoma.

Surprisingly, actinic keratoses are often not related to their neighboring cSCC. Spatial analyses reveal gene expression heterogeneity, including checkpoint molecule enrichment at invasive fronts, highlighting tumor and immune cell interactions.

Mucosal and vulvovaginal melanomas are biologically and clinically distinct from cutaneous melanoma and continue to have poor survival outcomes. Their rarity restricts high-quality evidence, highlighting the need for collaborative, innovative research to inform effective treatment strategies.

In the context of the imaging and molecular study results, a diagnosis of giant cellular blue nevus was made. This case highlights a rare presentation of giant CBN and the utility of integrating next-generation sequencing with histopathologic evaluation to distinguish the latter from melanoma and support clinical decision making.

Overall, combined srWGS-lrWGS facilitated the precise determination of SVs between CYP2A6 and CYP2A7. This approach could contribute to SV identification in highly homologous chromosomal regions and elucidation of functions of germline SVs in cytochrome P450 in lung cancer.

CGP revealed actionable alterations in most patients with advanced GISTs; however, its impact on treatment decisions remains limited under current practice. Early CGP implementation may facilitate access to matched therapies or clinical trials, enabling prognostic stratification in patients with advanced GISTs.

The tGEP analysis unveiled a macrophagic infiltration, with a pro-inflammatory M1-type polarization, in the context of lack of PD-L1 expression. The response to nivolumab in a germline NF1-driven ARMM case seems independent from levels of TMB and PD-L1 expression and may be mediated by inflammatory response induced by M1-polarized macrophages.