PD-L1 overexpression

Combination of nivolumab and nintedanib was shown to be safe and feasible. Despite missing synergistic effects on efficacy for the overall population, promising OS was observed for patients with high PD-L1 expression and for patients with previous immunotherapy. Therefore, CPI responsiveness may have been restored in some cases. Inhibition of FGFR-mediated tumor progression seems relevant in tumors with lower levels of both PD-L1 and FGFR1 expression and might be effectively inhibited by nintedanib. The combination nivolumab/nintedanib might warrant further exploration in selected patients.

A moderate positive correlation was observed between PD-L1 expression and FDG uptake (R2 = 0.36) and a weaker correlation with FAPI uptake (R2 = 0.19). This Multi-parametric imaging can enhance immunohistochemistry, aiding in patient stratification for immunotherapy and overcoming the limitations of single-site biopsies.

High PBK expression was associated with longer OS and RFS and remained an independent favorable prognostic factor in multivariate analysis. PBK expression in CRC is linked to proliferative tumor epithelial states, an immune-activated microenvironment, and favorable outcomes, supporting its utility as a prognostic biomarker.

Moreover, we underlined that high PD-L1 expression level is associated with more aggressive thymoma subtypes and may have a role as a prognostic biomarker. These findings support the need for further studies on the potential role of molecular and predictive pathology in thymic epithelial tumors.

The patient received first-line osimertinib combined with pemetrexed/cisplatin, achieving durable disease control for 17 months...Treatment was switched to alectinib, leading to significant tumor regression and partial response. This case illustrates that in triple-positive NSCLC, initial EGFR-TKI combined with chemotherapy can achieve long-term control, while dynamic molecular profiling at progression is essential for identifying resistance mechanisms. Sequential targeted therapy guided by NGS remains a cornerstone for precision management in this complex molecular subtype.

TROPION-Lung10 (NCT06357533) is a phase 3, open-label, multicenter, randomized study evaluating the efficacy and safety of first-line Dato-DXd plus rilvegostomig versus standard-of-care pembrolizumab in patients with advanced/metastatic nonsquamous NSCLC with PD-L1 TC expression ≥50% and without AGAs. TROPION-Lung10 will assess first-line Dato-DXd plus rilvegostomig in patients with advanced/metastatic NSCLC with high PD-L1 expression and without AGAs. ClinicalTrials.gov, identifier NCT06357533.

High PD-L1 expression in EGFRm NSCLC is associated with more aggressive morphologic features and modifies the association between post-progression ICI and survival. These findings support PD-L1-informed selection after EGFR-TKI failure, while prospective confirmation is needed.

Our findings suggest that CD274 alterations, PD-L1 expression on tumor cells and TILs, BRAF mutations, genomic amplifications, and tumor mutational burden may provide meaningful prognostic information in patients with melanoma. Prospective validation in larger cohorts is warranted to confirm the utility of these markers in guiding therapeutic decisions.

Among different gene alteration subgroups for advanced NSCLC, the efficacy of first-line ICIs did not differ with statistical significance, with high PD-L1 expression as a predictive factor for better survival. In KRAS mutant patients, KRAS G12C mutation or TP53 co-mutation might indicate improved survival.

This study underscores the diverse genetic mutations occurring in NSCLC patients with varying risk factors. The identification of TP53 co-mutations provides critical insights for personalized immunotherapeutic strategies and optimizing treatment outcomes.

In vivo, anlotinib reduced tumor growth in Sh-PD-L1-OR models (P < 0.01), with decreased expression of EGFR, PD-L1, YAP, and β-catenin. These findings suggest that high PD-L1 expression promotes osimertinib resistance through activation of YAP and Wnt/β-catenin, and that anlotinib combined with osimertinib can reverse resistance by restoring GSK3β activity, activating the Hippo pathway, and inhibiting β-catenin signaling.

In this case, the treatment comprised SBRT 24 Gy/3 fractions → q21d toripalimab 240 mg + nab-paclitaxel 200→100 mg + anlotinib 12 mg d1-14, with continuous Bifidobacterium triple viable tablets. These results challenge the prevailing assumption that pMMR status invariably predicts resistance to immunotherapy. These findings suggest that, in pMMR pancreatic cancers with high PD-L1 CPS, multimodal treatment strategies may remodel the tumor microenvironment and overcome immune resistance, highlighting a promising therapeutic direction.