TMB-L

Beyond this, both tumours present remarkably low tumour mutational burdens and were microsatellite stable though one sample also showed chromosomal instability with high levels of inversions and a ploidy level of 2.8 which has not been well characterised in SCCO patients. This report contributes towards the small number of cases of SCCO that are currently documented and have their genome characterised in the literature.

Emerging platforms, including oncolytic virotherapy, NK cell engagers, and neoantigen vaccines, offer rational strategies to convert immunologically cold tumors into treatment-responsive phenotypes. Together, these advances point toward a future of combination immunotherapy tailored to the distinct immune biology of childhood cancers.

In silico drug sensitivity analysis further suggested that high-risk patients may develop poorer sensitivity to five clinical drugs, including Cisplatin, Oxaliplatin, and Vinorelbine. The six-m7G-related-lncRNA signature represents a promising prognostic tool for EGC that may facilitate personalized risk stratification and guide clinical decision-making regarding adjuvant or immunotherapeutic strategies.

Moreover, the absence of off-target cross-reactivity was proved by peptide mutagenesis, highlighting the specificity of the TCR for CTSG. These results reveal the potential of dual restricted TCRs, and of CTSG-TCR T cells as powerful therapeutics for a broad AML patient population.

We discuss the challenges associated with their validation and clinical translation, as well as their relevance for the development of vaccines and adoptive T cell-based therapies. Finally, we illustrate these concepts using epithelial ovarian cancer as a representative model of low-mutational-burden tumors, where lncRNA-derived neoantigens may help overcome current limitations of immunotherapy and enable patient stratification for personalized treatment approaches.

Potential responses to immune checkpoint blockade (ICB) and 5-fluorouracil (5-FU) chemotherapy were further inferred using established computational frameworks...Further analysis suggests that CRC patients with lower SUMOscore might be more sensitive to immune checkpoint inhibitors and 5-FU chemotherapy. The SUMOscore captures clinically relevant TME heterogeneity in CRC and may help guide selection of immunotherapy and adjuvant chemotherapy.

Functionally, treatment with a PKM inhibitor significantly suppressed lactate production. This study reveals that TIMP1 promotes immunosuppression and PKM-LDHA drives metabolic reprogramming in CRC.

These findings establish LGMS as a genomically stable, epigenetically distinct myofibroblastic sarcoma driven by USP6 overexpression and an inflammation-enriched transcriptome. They support its recognition as a standalone entity, facilitate integration into methylation-based sarcoma classifiers for improved diagnostic precision, and nominate USP6-associated pathways and immune checkpoint blockade as promising therapeutic strategies for recurrent or unresectable disease.

Furthermore, we critically assess how standard of care (ADT, chemotherapy, radiotherapy) and emerging agents (PARPi, HDACi) reprogram the immune landscape with time-dependent, often paradoxical effects. Finally, we propose a roadmap for precision oncology, emphasizing that future success lies in "ecological editing"-biomarker-driven patient stratification and rational combination strategies to overcome the physical and biological barriers of the TME.

FOLR1 expression in the two cases was weak and below currently used clinical cutoffs for mirvetuximab soravtansine eligibility...Only a subset of anaplastic carcinomas of the ovary express targetable tumor antigens at low levels, suggesting that these may have limited benefit from antibody-drug conjugates. Likewise, due to mismatch repair proficiency and low tumor mutational burden, immunotherapy is unlikely to be effective in this rare disease.

Thus, Indel rate, particularly in combination with TMB, may be a promising predictive biomarker for gastric cancer. However, further validation of their predictive value is warranted.

Functionally, PGAP3 silencing significantly impaired proliferation, clonogenic growth, and migration in vitro. Our findings identify PGAP3 as a tumor-intrinsic gene associated with metabolic reprogramming and a CTL/CD8+-low immune contexture in PCa, supporting PGAP3 as a potential marker of the immune-cold tumor microenvironment and motivate future mechanistic studies in immunocompetent systems.