TMB-L

We establish a robust, mutation-independent methylation-based liquid biopsy strategy for neuroblastoma that enables accurate, quantitative disease monitoring across all high-risk patients including those lacking trackable genomic alterations. This approach supports clinical translation of methylation-based cfDNA deconvolution as a broadly applicable platform for pediatric precision oncology.

APOBEC mutational signatures represent a robust predictive biomarker for ICI response in TMB-low metastatic NSCLC, identifying responders particularly among PD-L1-negative patients where biomarker guidance is most needed, detectable from targeted gene panels used in routine clinical practice.

Testicular germ cell tumors (TGCTs) are the most common solid malignancies in young men and, despite high cure rates with cisplatin-based multimodal therapy, a clinically relevant subset of patients develops relapsed, platinum-refractory, or treatment-resistant disease with limited salvage options and substantial long-term morbidity...We argue that the next phase of the field should move beyond descriptive biomarker studies toward mechanism-based, TGCT-specific translational strategies integrating miRNA mimics, antagomirs, extracellular vesicles, or miRNA-augmented cellular therapies with immune-priming approaches such as epigenetic therapy, radiotherapy, vaccines, or CAR-T platforms. Such a framework could enable more precise biological stratification and improve the efficacy, durability, and tolerability of immunotherapy in refractory TGCT.

Collectively, the data support a shift from single-analyte biomarkers toward integrative, dynamic, systems-level models for patient selection, heralding a new era of precision immune-oncology in GC. However, most emerging biomarkers remain investigational and require prospective validation.

Treatment of human sarcoma lines with decitabine and entinostat induced similar gene expression changes, including shared antigen targets, and increased MHC I expression. These findings demonstrate that epigenetically upregulated antigens can serve as effective tumor-specific targets and broaden immunotherapy strategies for low-mutation sarcomas.

This study reveals the unique molecular landscape of EBV+ IFDCS, characterized by frequent NQO1 mutations and activation of key oncogenic pathways. These findings provide critical insights into the tumor's pathogenesis and suggest potential molecular targets for future therapeutic strategies.

Checkpoint inhibitors are also under evaluation, particularly in combination with immunomodulatory or targeted agents. Collectively, these trials highlight both the promise and limitations of immunotherapy in pediatric sarcomas and underscore the need for deeper understanding of sarcoma immune biology to guide future, more effective therapeutic strategies.

LA-R/M ACC has a low TMB profile overall. Median TMB was higher in NOTCH-activated ACC in both the NHS and MSK groups and TMB may have value in further stratifying patients with LA-R/M ACC.

These findings provide proof-of-concept that site-directed RNA editing can be used to reprogram tumor immunogenicity by generating defined neoantigen-like epitopes from shared tumor-associated antigens. This strategy may expand neoantigen-based immunotherapy beyond tumors with high mutational burden and warrants further investigation for clinical translation.

Our work is the first to demonstrate that non-canonical antigens drive immunogenicity in low-mutation RCC, thereby resolving a key question in cancer immunology-how tumors with low mutational burden can provoke robust T-cell responses.

Meanwhile, cDC1-mediated antigen spreading induced by ILvax enabled the expansion of adoptive TCR-T while shifting TCR-T metabolism toward oxidative phosphorylation (OXPHOS). Localized tumor administration with ILvax simultaneously enhances the functionality of both endogenous CD8+ T cells and adoptive TCR-T cells, offering a clinically translatable collaborative strategy against pancreatic cancer.