TMB-H

This retrospective, single-center cohort study used the Research Patient Data Registry (RPDR) to identify adults with breast cancer, lung cancer, renal cell carcinoma, or melanoma who received PD-1 inhibitor monotherapy (pembrolizumab or nivolumab) between January 1, 2000, and May 29, 2024. Higher TMB and enrichment of selected tumor mutations may reflect a tumor immunogenicity state that predisposes to pituitary autoimmunity under PD-1 blockade. These findings provide a hypothesis-generating genomic framework for future studies of endocrine irAE risk stratification.

We propose a framework in which hepatocytes dedifferentiate into BPs as a pre-malignant state, undergo malignant transformation, and a subset acquires stemness through DNMT-mediated reprogramming stabilized by epigenetic memory. These findings challenge the classical stem cell origin hypothesis, showing that CSCs in established HCC are late-stage dedifferentiation products, provide a rationale for targeting CSC epigenetic stability, and offer a biomarker for early recurrence.

Targeted next-generation sequencing demonstrated high tumor mutational burden (>10 mutations/Mb) and 2 common driver mutations [TP53 (c.853G>A) and TERT (c.-146C>T)]. This is the first report of an HPV-independent cervical SCC with choriocarcinomatous differentiation, supporting a clonal origin with divergent differentiation, and suggesting comprehensive therapies combining immunotherapy and pathway inhibitors for this aggressive cancer.

A positive correlation was found between TIL score and TNM stage. Intermediate and high TIL scores were common in advanced stages, whereas low TIL scores were prevalent in early stages. The findings suggest that advanced tumors may harbor higher mutation burdens and immunogenicity. Future research should explore the molecular subtypes of immune profiles.

The signature independently predicted prognosis (AUC: 0.70-0.84) and treatment response: LR patients favored immunotherapy (lower TIDE, higher IPS), while HR patients were sensitive to chemotherapy (e.g., Bosutinib, Tozasertib). This transcriptome-derived m6A-associated prognostic model can effectively predict clinical survival outcomes and therapeutic response in LUAD patients. Combined with immune landscape, genomic mutation profiles and single-cell transcriptomic evidence, this signature provides a reliable basis for personalized risk stratification and rational treatment choice.

P1/2, N=121, Active, not recruiting, Precision Biologics, Inc | Recruiting --> Active, not recruiting | Trial completion date: Jan 2029 --> Nov 2026 | Trial primary completion date: Jan 2028 --> Jun 2026

We demonstrate that TMB is dynamic and rises over time and with select treatment exposures. These findings reinforce how TMB should be interpreted within the broader context and not necessarily viewed as a standalone threshold for initiating immunotherapy in advanced prostate cancer.

We propose that future progress will likely depend on mechanism-based, biomarker-driven approaches that match specific immune evasion patterns with rationally designed interventions, with the goal of extending immunotherapy benefits to broader CRC populations. This narrative review synthesizes peer-reviewed literature from PubMed and clinical trial registries (2015-2025), prioritizing Phase II/III trials and mechanistic studies.

Outcomes appear to be influenced by an interplay of disease context, clonal architecture, and therapeutic strategy rather than individual mutations alone, underscoring the need for integrated molecular profiling and prospective studies to guide management. This study highlights that MS with MR mutations may follow different cellular pathways to evolution.

We present a renal transplant recipient with metastatic small bowel adenocarcinoma harboring a POLE mutation who was treated with pembrolizumab and achieved a complete metabolic response on PET-CT with negative circulating tumor DNA. This case suggests that immune checkpoint inhibitors may be considered in carefully selected transplant recipients with high tumor mutational burden, though risks remain.

We also highlight clinically relevant biomarkers, including MSI/MMR status, tumor mutational burden, immune contexture, Immunoscore, circulating tumor DNA, microbiome profiles, and spatial or AI-assisted multi-marker models. This review summarizes emerging strategies to enhance therapeutic efficacy in CRC and maps each modality to the tumor-intrinsic or tumor-extrinsic resistance barriers it is most likely to overcome.

P1/2, N=55, Recruiting, University of Chicago | Not yet recruiting --> Recruiting