TMB-H

P1/2, N=55, Not yet recruiting, University of Chicago | Initiation date: Jan 2026 --> Dec 2026

P1/2, N=130, Recruiting, Grey Wolf Therapeutics Limited | N=65 --> 130

© 2026 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland

The patient initially presented with a destructive iliac mass in 2021 and underwent induction with doxorubicin/cisplatin, which was complicated by acute kidney injury and thromboembolic events, followed by hemipelvectomy...Treatment with high-dose ifosfamide provided no durable disease control, and imaging demonstrated progressive growth...Resection in June 2022 demonstrated no viable tumor, consistent with complete pathologic response. The patient has since completed one year of adjuvant pembrolizumab, with ongoing therapy and no evidence of recurrence at 24 month follow-up.

This review summarizes the current research status of lung cancer vaccines, clarifies the unique therapeutic advantages of mRNA vaccines compared to traditional vaccine modalities, and highlights existing challenges associated with mRNA vaccines. It also provides an overview of current clinical trials of mRNA vaccines for lung cancer and proposes rational design and clinical application strategies for personalized mRNA vaccines within the framework of precision oncology, based on evidence-based medicine.

Together, our findings identify promising therapeutic and prognostic targets linked to CDK4-amplification in CKS. These biomarkers warrant further investigation and may ultimately contribute to improved clinical outcomes for patients with CKS.

Tumor location in CRC correlates with distinct molecular patterns. Right-sided tumors are associated with dMMR, MSI-H, and higher TMB, while left-sided CRCs display more ERBB2 alterations and class 5 APC mutations. The results highlight the importance of integrating tumor location into personalized molecular diagnostics and therapeutic planning for CRC patients.

Despite its simplicity, the model reveals a rich phase space, including an evolutionary bimodal regime where both immunologically silent and mutationally active strategies are locally optimal for tumor growth. Notably, the model illustrates two key eco-evolutionary mechanisms of resistance to immunotherapy: preexisting resistance, driven by the persistence of silent clones within tumors with high mutational burden; and immunoediting, where immune pressure selects for reduced antigenicity over time.

P1, N=30, Recruiting, National Cancer Institute (NCI) | Trial completion date: Jan 2027 --> Jan 2028 | Trial primary completion date: Jan 2026 --> Jan 2027

Finally, we discuss translational strategies to overcome immunotherapy resistance and outline a precision immunotherapy roadmap, arguing for biomarker-guided and subtype-stratified clinical trial design. By synthesizing mechanistic, translational, and clinical perspectives, this review provides a framework for rational therapeutic innovation in SCLC.

Immunoscore Immune-Checkpoint (ISIC)-high tumors (52% of the samples) shared a similar microenvironment composition to IS-high and TuLIS-like high tumors and displayed higher mutational burdens than ISIC-low tumors. In conclusion, a substantial proportion of MSS RASmt CCs exhibit high ISIC scores, meriting evaluation in prospective trials of immunotherapy-based combination regimens.

WES revealed a high TMB in both the primary tumor tissue (43.0 mut/Mb) and the TC717 cell line (34.0 mut/Mb), and pathogenic TP53 c.614A > G and BRAF c.1574 T > C variants, neither previously reported in ASC. TC717 provides a valuable preclinical platform for investigating sinonasal ASC biology and for evaluating genotype-directed therapies.