TMB-H

Multivariate Cox regression analysis identified clinical stage as an independent predictor of overall survival, with patients at stages Ⅲ-Ⅳ exhibiting poorer prognosis (HR=5.359, 95% CI: 1.124-25.546). BRCA-mutated colorectal tumors exhibit lower invasiveness, higher TMB-H rates, and abundant immune cell infiltration in the tumor microenvironment, suggesting that patients with BRCA-mutated colorectal cancer are more likely to benefit from immunotherapy.

A biopsy of the neck mass confirmed recurrent thymoma, type B3, and her disease progressed despite platinum-based chemotherapy and subsequent pemetrexed treatment. This case demonstrates a favorable outcome with biomarker-directed ICI treatment in recurrent thymoma with limited treatment options, highlighting the importance of appropriate molecular markers to predict drug response. Although TMB-based immunotherapy is FDA-approved in the U.S., it remains unavailable in Korea, underscoring the need to explore flexible access pathways, including the potential use of immunotherapy beyond current indications, to improve treatment options for patients with life-threatening conditions.

These results contrast with prior tissue-based studies and indicate that bTMB may reflect tumor burden and aggressive disease biology rather than tumor immunogenicity. Prospective studies integrating bTMB with ctDNA fraction, tumor burden metrics, and longitudinal molecular dynamics are warranted to refine its clinical utility.

Early acquisition of chromosomal copy-number alterations in CN-type thymomas further supported different evolutionary paths among subgroups. Together, these findings provide insights into the cellular origins and tumorigenic processes of TETs and underscore the value of integrative genomics for accurate cancer classification.

The frequency of TMB-high was 4.4%, which is slightly higher than that previously reported. Pembrolizumab demonstrated greater efficacy in patients with MSI-H plus TMB-high while also exhibiting some efficacy in patients with MSS plus TMB-high.

Analyses in SCLC cell lines and mouse models shows that depletion of DNAPKcs leads to proteasomal degradation of MYC via GSK3β pathway. We show that DNAPKcs upregulation contributes to immunotherapy resistance and DNAPKcs inhibition represents a promising therapeutic strategy to induce antitumor immunity and potentiate immunotherapy efficacy in immunologically suppressed SCLC.

High TMB in patients with PDAC portends better PFS, particularly those receiving combination immunotherapy. A clinically applicable TMB cutoff of 5 mut/Mb was identified, stratifying patients into biologically distinct low- and high-TMB prognostic groups. DLCT-derived pancreatic phase normalized iodine concentration emerged as a superior noninvasive TMB biomarker compared to conventional imaging parameters.

Cross-cohort analysis further revealed that despite favorable immunological features (higher TMB, neoantigen load, memory-activated CD4+ T cells, activated NK cells, mast cells, M1 macrophages and immune checkpoint expression), MSI-H gastric cancers have heterogeneous immunotherapy outcomes. Collectively, dMMR/MSI-H status alone is insufficient for outcome prediction, highlighting the need for individualized TIME evaluation in patients with gastric cancer receiving immunotherapy.

This study underscores the diverse genetic mutations occurring in NSCLC patients with varying risk factors. The identification of TP53 co-mutations provides critical insights for personalized immunotherapeutic strategies and optimizing treatment outcomes.

In this study, we characterized resistance mechanisms using the clinical candidate HRO761 and two novel inhibitors in MSI cell lines and xenograft models...This chemotype-specific resistance profile suggests opportunities for developing next-generation inhibitors that retain activity against resistant variants and for implementing rational treatment strategies with existing inhibitors. Overall, our findings demonstrate that on-target resistance to WRN inhibitors emerges rapidly in dMMR backgrounds but also highlight potential approaches to overcome resistance, supporting continued development of WRN-targeted therapies for MSI cancers.

Based on these findings, pembrolizumab was initiated as first-line therapy...Our findings underscore that alternative biomarkers, such as somatic mutations in DNA repair genes including MSH2 and ATM, may predict unexpected responses to immune checkpoint blockade and inform therapeutic decisions, even in the context of MSS and borderline TMB. Broader implementation of molecular profiling is warranted to identify such patients.

The exploration of molecular characteristics and subtypes of bladder cancer and the development of new drugs and treatment strategy have also stimulated more clinical studies of bladder cancer. Here, we review advances in the treatment of bladder cancer and clinical practice of next-generation sequencing, highlight important advances in immunotherapy for bladder cancer, preliminarily summarize molecular features of bladder cancer for clinical practice, and came up with direction for future treatment development.