TMB-L

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.

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.

Frequent synaptophysin expression in SMARCA4-deficient UC of the oesophagus can lead to diagnostic confusion with neuroendocrine carcinomas, resulting in potential mismanagement. BRG1 IHC should be incorporated in the diagnostic workup of poorly differentiated oesophageal tumours to ensure accurate classification and guide effective treatment strategies.

Given the indolent nature of many screen-detected LCINS, there is a need to shift the clinical mindset toward prioritizing active surveillance instead of immediate surgery. Overall, LDCT screening for LCINS requires careful balancing of potential benefits and harms, underscoring the need for tailored, evidence-based strategies.

We also found that MSS tumors with high TMB have a substantially higher number of neoantigens compared to low-TMB MSS tumors, suggesting they may respond better to immunotherapy, including a high proportion of predicted high-affinity neoantigens. These findings support the clinical relevance of TMB as a biomarker for neoantigen prediction and immunotherapy-relevant features in MSS tumors.

Recent advances in multi-antigen targeting, metabolic reprogramming, and innovative delivery strategies have enhanced preclinical efficacy, while the integration of emerging biomarkers such as ADAMTSL4, ACSS3, and radiomics-derived immune signatures offers opportunities for precision patient stratification. Converging developments in real-time molecular monitoring, spatial immunoprofiling, and rationally designed combination regimens hold the potential to recalibrate the glioma immune landscape, paving the way toward clinically impactful and durable immunotherapeutic responses.

This approach resulted in unprecedented survival outcomes: the 72-month overall survival dramatically exceeds the median OS of less than 12 months reported for advanced PSC, and the patient maintained a progression-free survival of over 37 months on combination therapy, surpassing historical PFS benchmarks. This case provides a clinically actionable framework for managing multi-driver mutated, immunoresistant PSC.

Our study suggests that PAEP may be a potential therapeutic target for ccRCC, providing a new theoretical basis for ccRCC clinical immunotherapy.

This case underscores the diagnostic challenges of MLA, particularly its ability to masquerade as low-grade or high-grade serous carcinoma on morphology, including cytology, frozen, and permanent sections. We compare the cytologic, histologic, immunophenotypic, and molecular features of MLA and serous carcinoma, highlighting the importance of thorough evaluation to avoid the pitfall of morphology-only diagnosis.

Three patients with locally advanced conjunctival squamous cell carcinoma originating in the inferior fornix were treated with immunotherapy: a 74-year-old male was treated with 4 cycles of cemiplimab, a 54-year-old female was treated with 3 cycles of pembrolizumab, and a 69-year-old female was treated with 2 cycles of pembrolizumab. Review of the literature reveals 18 cases of invasive conjunctival squamous cell carcinoma treated with immunotherapy in addition to the 3 cases reported herein, with tumors of responders tending to have a higher tumor mutational burden than those of nonresponders. There is increasing evidence that conjunctival squamous cell carcinoma originating in the sun-protected inferior fornix/inferior palpebral conjunctiva has low tumor mutational burden and is less likely to respond to immunotherapy than squamous cell carcinoma of bulbar conjunctival origin.

Our study described the characteristics of composite renal tumors combining WT and RCC, highlighting several unusual and specific features. Its behavior appeared to be more aggressive than that of WT or RCC alone, and we propose that it should be recognized as a separate entity, which may require different treatment from WT or RCC alone.

The inguinal region of young males appears to be one of the favored sites for these tumors. Furthermore, NGS-based algorithms may fail to accurately classify such tumors.