TMB-H

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.

AlphaTMB improves survival prediction beyond TMB alone, better captures immunogenic tumor profiles, and reflects more accurate patient stratification. This AI derived somatic mutations pathogenicity scoring represents a step toward personalized immuno-oncology and merits further validation in prospective studies.

A super-high TMB threshold of ≥ 25 mut/Mb by MSK-IMPACT identifies a distinct subset of melanoma patients who achieve truly exceptional benefit, with nearly one in two attaining clinical cure following ICB therapy. These data support prospective validation of "hypermutation" as a clinically actionable biomarker, refine patient counseling, and inform trial stratification in the era of personalized cancer immunotherapy.

Combining biomarker-driven immunotherapy and targeted approaches such as PD-1 blockade in MSI-H or EBV-positive tumors, HER2-directed therapy, and CLDN18.2 inhibition, has demonstrated a paradigm shift in the clinical management. This review highlights a pathologist-centered perspective on molecularly defined subgroups, actionable biomarkers, and evolving therapeutic paradigms in CRC and GEJ carcinoma, advancing precision oncology.

On the other hand, agent-based models (ABMs) naturally capture stochasticity, interactions at an individual level, and discrete events that lie beyond the scope of differential-equation formulations. As such, we also convert our ODE model, with parameters calibrated to experimental data, to an ABM, preserving its dynamics while providing a flexible platform for future mechanistic investigation and modelling.

Clones were injected subcutaneously or intracranially with or without anti-PD-1/anti-CTLA4 and dexamethasone...Rather, rejection depended on increased secretion of pro-inflammatory chemokines. Msh2 and Mlh1 loss was not equivalent, suggesting that additional studies are needed to elucidate germline and somatic mismatch repair gene-specific immune alterations.

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.

P1, N=10, Recruiting, Cancer Hospital Chinese Academy of Medical Sciences; Guangzhou Celling Biological Technology Co., Ltd.

We demonstrated that opportunistic pathogens exhibited higher infection rates in patients with TP53-mutated, TMB-H, and non-EGFR-mutated tumors. Microbial infection in patients with EGFR mutations might be an influencing factor that weakens the therapeutic efficacy.

These findings support the clinical utility of TMB as a biomarker for predicting ICI response in routine oncology practice. In particular, excluding hotspot mutations from TMB calculations may improve response prediction in patients whose TMB values are near the threshold.

Over 3 months, MRI showed further regression of the primary lesion and nodal disease, and PSA and SCC decreased. In metastatic CRPC harboring a BRCA2 mutation and near-threshold TMB, olaparib produced clear radiological and serological responses.