TMB-H

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.

Baseline MSAF is an independent prognostic biomarker in metastatic GC and may reflect underlying biological aggressiveness. Incorporating MSAF into risk stratification frameworks could enhance prognostic classification and inform personalized treatment strategies.

Postoperatively, the patient received 4 cycles of XELOX chemotherapy plus nivolumab, followed by consolidative radiotherapy synchronized with capecitabine and nivolumab, and subsequent maintenance therapy with capecitabine and nivolumab until sustained no evidence of disease (NED) was confirmed in January 2023. This exceptional and sustained response may be attributed to the synergistic effect of TMB-H and POLD1 mutation, which enhance neoantigen generation and sensitize tumors to immunotherapy. This case highlights the potential of biomarker-driven chemo-immunotherapy combined with MDT-guided multimodal treatment (surgery + adjuvant therapy + consolidative radiotherapy) to achieve curative intent in patients with metastatic GMC, providing valuable insights for personalized treatment strategies in this poor-prognosis population.