TMB (Tumor Mutational Burden)

Our work defines a chemotherapy-resistant and metastasis-enriched malignant epithelial subpopulation in PDAC that drives disease progression through an immune-cold niche. We identify RARRES1 as a pivotal regulator of this process, contributing to both therapy resistance and immune exclusion, and propose it as a novel pan-cancer prognostic biomarker. These findings reveal a targetable cellular mechanism underlying poor treatment response in PDAC.

However, the pharmacological targets, optimal combinations, and predictive biomarkers for ginsenoside-based adjuvant therapy remain poorly defined. Integration of systems pharmacology, single-cell technologies, and modern clinical trial design will be essential to clarify the role of ginsenosides as partners in immunotherapy for GI cancers.

In the NASIR-HCC trial, patients with hepatocellular carcinoma (HCC) received selective internal radiation therapy and the anti-PD-1 antibody Nivolumab, but many of them did not achieve clinical benefit (B)...Finally, polyepitopic peptide vaccination containing neoAgs from an NB patient induced stronger and broader T-cell responses compared to polyepitopic DNA vaccine. Our results demonstrate the immunogenicity of neoAgs in our cohort, supporting their potential utility in therapeutic vaccines designed to boost antitumor immunity.

Despite compelling mechanistic rationale, clinical translation remains hindered by inadequate biomarker integration, heterogeneous clinical trial design, and discordance between biological endpoints and survival outcomes. Collectively, these advances delineate a transition from empiric combination therapy toward immune-centric precision immuno-oncology in HNSCC, underscoring the necessity for biomarker-driven trial design, longitudinal immune monitoring, and multidisciplinary collaboration to translate mechanistic synergy into durable clinical benefit.

Analysis across patients with melanoma, breast cancer or renal cancer demonstrated pan-cancer relevance. Together, these findings identify thymic health as a previously unrecognized, tumour-agnostic determinant of immunotherapy efficacy, with potential implications for patient stratification, treatment timing and the development of immune-rejuvenating strategies in precision immuno-oncology.

Additionally, high WDHD1 levels were associated with increased CD4 memory T cell infiltration, elevated tumor mutational burden (TMB), and enhanced expression of key immune checkpoint markers, suggesting a potential for improved response to immunotherapy in these patients. These findings suggest WDHD1 as a novel oncogenic driver and promising therapeutic target in HCC.

Young patients with DPM have strong personal and family histories of cancer, and heterogeneous somatic and germline alterations, indicating divergent underlying biology. With the increasing prevalence of young adults with cancers, mesotheliomas, although uncommon, should be on the differential for patients even without asbestos exposure history in this age group.

Nomograms developed by integrating clinical features and risk scores displayed high predictability. The findings provide new molecular markers and potential therapeutic targets for the prognosis of LUAD and lay a theoretical foundation for the development of therapeutic approaches targeting the NECSO mechanism in patients with LUAD.

Over the past decade, multiple ICIs have demonstrated meaningful clinical activity, and their indications have expanded across treatment lines, including second-line therapy after platinum, first-line therapy for cisplatin-ineligible disease, avelumab maintenance following chemotherapy, and, more recently, combination strategies such as pembrolizumab plus enfortumab vedotin. In this review, we provide a comprehensive overview of currently established and emerging biomarkers of ICI response in UBC, including PD-L1 immunohistochemistry, serum inflammatory markers, tumor mutational burden, histology and molecular subtypes, gene expression patterns and microbiome features. We discuss their strengths, limitations, and potential translational relevance, highlighting ongoing challenges and future directions.

Our collective findings suggest that ADCY4 holds promise as a potential prognostic biomarker and a novel target for cancer immunotherapy.

Finally, we review rational therapeutic strategies such as vascular endothelial growth factor-tyrosine kinase inhibitors-ICI combinations, radiotherapy-ICI approaches, perioperative immunotherapy, and emphasize the need for biomarker-enriched trial design. TETs provide a powerful model to understand how failure of central tolerance can simultaneously sensitize tumors to immune attack and prime patients for catastrophic toxicity, with implications that extend to other low-TMB, immune-infiltrated malignancies.

We also found that karyotype has limited utility in the setting of NB. Based on this data, we developed an institutional workflow for NB, including MYCN FISH, CMA, and NGS.