PD-L1 overexpression

Tumor PD-L1 is associated with better PFS and OS after ipilimumab + nivolumab. In the sarcomatoid/rhabdoid subset, lower CD25 (a marker of regulatory T cells) was associated with improved PFS, while increased neutrophil infiltration (CD66b+/MPO+) emerged as a novel feature of sarcomatoid/rhabdoid tumors, which may be harnessed for therapeutic benefit in this population.

Based on clinicians' practical deployment, the DHGN significantly reduced the operational complexity and computational requirements (P < 0.01) for model development and application in clinical settings. In conclusion, we proposed a clinician-friendly population graph model that fuses baseline clinical data with CT radiomics on widely available CPU hardware accurately stratifies NSCLC patients for immunotherapy benefits, potentially redefining benchmarks for non-invasive prognostic biomarkers and enabling broader clinical translation.

Silencing SH3PXD2A-AS1 reduced MYBL2/WTAP/PD-L1 signaling, decreased malignant phenotypes in vitro, and restored antitumor T-cell activity in humanized mouse models, whereas enforced MYBL2 or WTAP expression counteracted these effects. Collectively, these findings define an lncRNA-transcription factor-epitranscriptomic checkpoint that sustains PD-L1-mediated immune escape in NSCLC, and nominate SH3PXD2A-AS1 and its MYBL2/WTAP partners as potential biomarkers and therapeutic targets to improve responses to immune checkpoint inhibition.

The findings of this study demonstrated a potential dual role of USP35 in NSCLC, contributing to the targeted therapy of the cancer.

Two cycles of nivolumab plus ipilimumab were performed before discovering severe cervical spine pain. Here we show (1) robust CD3+ and CD20+ infiltration in primary tumors and metastases, with immune cells in direct contact with tumor cells or organized in lymphoid aggregates/tertiary lymphoid structures; (2) PD-L1 overexpression in sRCC and nodal metastasis but absent in post-immunotherapy bone lesions; (3) increased CD163+ macrophages in sRCC and metastases versus ccRCC. This case illustrates that ICIs can induce near-complete eradication of bone metastases; that bone is not an immune-exempt organ, with massive intratumoral immune cell infiltration; and that immediate immune-mediated tumor clearance prevents structural skeletal damage, which merits careful surveillance.

First-line ICI monotherapy and dual ICIs did not significantly improve OS, PFS, and ORR compared with EXTREME. However, a discernible trend suggested a potential survival benefit for ICIs in patients with high PD-L1 expression.

Notably, in this context, PD-L1 expression does not reliably predict benefit from ICIs but, rather, serves as a marker of aggressive tumor biology and early resistance to EGFR-TKI therapy. Lastly, we discuss the therapeutic implications of these observations, outlining the rationale for biomarker-informed, risk-adapted treatment strategies, including EGFR-TKI-based combinations, while emphasizing the need for careful integration of immunotherapy and prospective validation.

Longitudinal cfDNA WES captured dynamic clonal remodeling under immunotherapy and anticipated radiological outcomes. These findings underscore the clinical necessity of integrating dynamic molecular monitoring by liquid biopsy to overcome the limitations of static PD-L1 assessment, refine therapeutic stratification, and identify early resistance mechanisms in advanced NSCLC.

A 73-year-old woman with epidermal growth factor receptor (EGFR) L858R-mutant lung adenocarcinoma (cT4N1M1a stage IV, programmed death-ligand 1 (PD-L1) high expression (60%)) received osimertinib as first-line therapy, but disease progression was observed after two months. She subsequently received second-line therapy with carboplatin, paclitaxel, and atezolizumab, followed by maintenance atezolizumab...This case demonstrates long-term survival achieved by combining surgical resection with resumption of ICI therapy for solitary adrenal oligoprogression during ICI maintenance therapy. The findings suggest that local treatment for limited progressive lesions during ICI therapy may be a useful therapeutic strategy.

Our results suggest that cPD-L1 expression in most sUC occurs secondary to IL6-JAK-STAT3 and interferon α/γ signaling. This provides a biologic rationale for evaluating response to immunotherapy in this patient population.

In conclusion, in addition to supporting histology grading of EM, our findings highlight that EM-HG cases display more heterogeneous expression profiles than EM-LG with some features in between EM-LG and SM/BM. Further data is needed to explore the potential clinical utility EZH2 IHC in the clinical management of pleural mesothelioma.

Reduced collagen deposition in HAS2⁺/⁻ tumors further underscores its role in tumor microenvironment remodeling. Targeting the HAS2-March4-PD-L1 axis through HAS2 inhibition, anti-PD-L1 therapy, or March4 overexpression suppresses tumor growth and improves survival.