PD-L1 underexpression

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.

TACTI-004 will evaluate whether efti can mitigate resistance to ICIs when added to SoC in NSCLC, irrespective of PD-L1 tumor status. www.clinicaltrials.gov identifier is NCT06726265.

HCC tissues with high PVR expression were more common in metastatic disease and were associated with an immune-cold TME. These findings may have implications for the development of immunotherapies for HCC.

While the correlation between treatment effects on PFS and OS was weak in ESCC, it was moderate in PD-L1-low GEA, and good in PD-L1-high GEA. Therefore, PFS is an adequate co-primary endpoint in future trials investigating novel ICIs-based regimens in GEA, especially if the analyses are pre-planned in PD-L1-high subgroups.

PD-L1 expression defines a biologically and clinically relevant subset of ATCs with distinct immune features and therapeutic vulnerabilities. Standardizing PD-L1 testing and integrating it with molecular and microenvironmental biomarkers will be essential to refine patient selection for immunotherapy and combination strategies, improving outcomes.

These findings suggest that LKB1 loss suppresses DPP4 expression, contributing to the immunosuppressive characteristics of the TME in KL-NSCLC cells, whereas restoring DPP4 expression promotes NK cell recruitment, facilitates immune activation, and enhances the effects of anti-PD-1 therapy. These results suggest that DPP4 is a key immune modulator and a promising therapeutic target, providing a novel strategy to overcome immune resistance and improve immunotherapy outcomes in this challenging subset of lung cancer.

In first-line chemoimmunotherapy-treated PD-L1-low/negative NSCLC, baseline LIPI can be used to independently stratify PFS and OS and identify a subgroup with poor prognosis. LIPI may support risk stratification at first-line treatment initiation. Prospective studies are warranted to validate these findings and optimize personalized treatment approaches.