PD-L1 overexpression

Bioinformatics analysis showed that YTHDF1 mRNA expression was significantly higher in LUSC tissues than in adjacent non-cancerous tissues (P0.05). YTHDF1 and YTHDF2 may serve as potential prognostic biomarkers and therapeutic targets, and YTHDF1-mediated m6A modification may open new avenues for LUSC immunotherapy.

Patients who underwent surgery after induction treatment achieved clinically meaningful survival gains. Our findings support the use of neoadjuvant immunotherapy with a response-adapted surgical strategy as a promising approach for unresectable stage III NSCLC.

One patient had a single brain metastasis and received comprehensive treatment including surgery, radiotherapy, chemotherapy, PD-1 inhibitor (tislelizumab), and PARP inhibitor (niraparib). The immune microenvironment characteristics of brain metastases (e.g., high PD-L1 expression, T-cell infiltration) may predict the efficacy of immunotherapy, but the prognosis for patients with multiple brain metastases remains poor. Further research is needed to explore the correlation between peripheral blood immune markers and treatment response in brain metastases.

In this cohort of surgically resected NSCLC, preoperative corrected serum calcium and smoking exposure were more closely associated with tumor metabolic activity than with specific molecular alterations. These findings suggest that simple clinical and biochemical parameters may provide complementary information, although their utility for discriminating individual molecular subgroups appears limited.

In multivariate analysis, independent prognostic factors associated with improved DFS included HPV16 infection, absence of PD-L1 overexpression, overexpression of CD4 and CD8, and combined chemoradiotherapy with cisplatin. These findings confirm the prognostic relevance of PD-L1, PD-1, and T-cell markers in HNSCC, particularly in HPV16-negative patients, and support further research into the use of these biomarkers in personalized treatment strategies.

Baseline differentially methylated fragments scores show a significant correlation with PFS, with low-risk patients demonstrating a longer median PFS compared to high-risk patients (11.4 months versus 6.9 months). Overall, first-line cadonilimab plus chemotherapy shows an encouraging efficacy with a manageable safety profile for challenging-to-treat PD-L1-negative advanced NSCLC, warranting further evaluation in controlled studies.

Baseline frequencies of peripheral CD4⁺ T TIGIT⁺ and CD8⁺ TEMRA cells were independently associated with survival outcomes in advanced NSCLC patients receiving first-line ICI-based therapy, suggesting that peripheral T cell immunophenotyping at treatment initiation may provide prognostic information beyond conventional biomarkers. Further studies incorporating external validation in independent cohorts, longitudinal immune profiling, and deeper T cell subset characterization are warranted to validate these findings and to elucidate the immune dynamics underlying treatment response and resistance.

Strebloside (3 mg/kg) outperformed AG490 and achieved efficacy equivalent to 5-fluorouracil (5-FU; 30 mg/kg) at one-tenth of the dose (n = 5 per group, P < 0.0001). Unlike AG490, which only blocks kinase activity, and 5-FU, which triggers compensatory p-JAK2 upregulation, strebloside induces complete JAK2 depletion with a favorable cardiac safety profile at the therapeutic dose. These findings establish JAK2 as a therapeutic vulnerability and position strebloside-mediated JAK2 degradation as a promising strategy to overcome immune evasion in EBV-associated malignancies.

KRAS Q61H and Q61L were the predominant mutational subtypes and demonstrated distinct molecular and clinical characteristics, with differences in co-mutational landscape and survival differences. Immunotherapy-based regimens were associated with more favorable outcomes compared to chemotherapy, particularly in patients with high PD-L1 expression, underscoring the importance of subtype-specific molecular characterization in clinical decision-making.

Experimental results demonstrate that TCM-NBs@PRO-mediated PD-L1 degradation significantly enhances CD8+ T cell infiltration and antitumor activity, while establishing durable protective immunity. By synergizing ultrasound-enhanced delivery, PROTAC-mediated PD-L1 depletion, and nanovaccine-driven T cell activation, this system overcomes the limitations of traditional vaccines and represents a promising approach for tumor immunotherapy with substantial clinical translational potential.

Combined stratification identified the longest PFS in high PD-L1 expression and low PD-1+CD8+ T cell infiltration (8.8 months) and the shortest in low PD-L1 and high PD-1+CD8+ T cell infiltration (3.5 months), supporting PD-1+CD8+ T cell infiltration might as a complementary biomarker to PD-L1. For OS, intratumoral CD8+ T cell density (HR 0.896; p = 0.011), clinical stage (HR 1.570; p = 0.025), and BMI (HR 0.935; p = 0.015) were independent factors.

Neoadjuvant nivolumab combined with platinum-based chemotherapy demonstrates favorable pharmacological efficacy, manageable toxicity and biomarker-driven therapeutic response in resectable NSCLC under real-world clinical conditions. These findings support the role of personalized immunopharmacotherapy and reinforce the clinical relevance of biomarker-guided drug selection in modern pharmaceutical oncology.