PD-L1 underexpression

These findings showed that NSD2 inhibits the progression of HCC by inhibiting the expression of PD-L1 through OXPHOS. Our results identify NSD2 as a tumor suppressor in the development of HCC.

PD-L1 expression on TIICs and dynamic NLR may be indicative of prognosis in BTC and could provide insights into immune status and response to immunotherapy after recurrence. These findings highlight the potential value of integrating local immune contexture with systemic inflammatory markers, but further validation in larger and prospective cohorts is warranted.

The resulting synergy between redox-driven cytotoxicity and immune modulation potentiates anti-PD-L1 efficacy, leading to robust tumor regression and durable immunological memory. Our work presents a seminal strategy that leverages tumor redox vulnerabilities to advance cancer immunotherapy, providing a new paradigm for overcoming ICB resistance via targeted tumor sensitization.

Preoperative treatment regimens containing immunotherapy, particularly the triple combination, improved pathological response without increasing preoperative risk. Tumor biology-especially Lauren subtype and PD-L1 expression-had a greater impact on response than regimen intensity, supporting biomarker-guided strategies.

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.

Patient-level data indicate that ESCCs with TPS < 1% and HER2-negative GEAs with CPS < 5 do not benefit from the addition of ICIs to conventional chemotherapy. More nuanced clinical trials and predictive biomarkers are warranted.

P3, N=1126, Active, not recruiting, AstraZeneca | Trial completion date: Dec 2025 --> Dec 2026

This approach resulted in unprecedented survival outcomes: the 72-month overall survival dramatically exceeds the median OS of less than 12 months reported for advanced PSC, and the patient maintained a progression-free survival of over 37 months on combination therapy, surpassing historical PFS benchmarks. This case provides a clinically actionable framework for managing multi-driver mutated, immunoresistant PSC.

Consistent with these findings, two patients derived profound clinical benefit from matched PARP inhibitors or anti-HER2 antibody-drug conjugate. Our findings definitively establish the somatic and clonal nature of these mixed tumors and provide a compelling rationale for molecularly guided treatment.

This could be an independent prognostic factor for RFS and OS with HR 1.889 and 1.990, respectively. PD-L1 expression levels can serve as a valuable predictor of outcomes in CCA patients, especially when evaluated alongside chemotherapeutic status.

We also discuss their translation and how these approaches may ultimately expand the benefit of immunotherapy to patients with treatment-refractory cancers. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Biology-Inspired Nanomaterials > Peptide-Based Structures Biology-Inspired Nanomaterials > Lipid-Based Structures.

Variations in PD-L1 expression were associated with the mean DNA index values exceeding 2.5 among the top 20 tumor cells analyzed. Compared with the non-expression group, the low-expression PD-L1 group demonstrated greater tumor cell invasiveness.