PD-L1 underexpression

P1/2, N=226, Active, not recruiting, Astellas Pharma Global Development, Inc. | Recruiting --> Active, not recruiting | N=366 --> 226 | Trial completion date: May 2028 --> Jun 2026 | Trial primary completion date: May 2028 --> Jun 2026

Taken together, this study demonstrates the prognostic value of the TIME using the three widely available markers CD3, CD8, and PD-L1 in PSCC. Furthermore, it provides additional evidence for a survival benefit of p16INK4A positive cases, compared to p16INK4A negative cases.

Nevertheless, SH2D1A remained significantly enriched in tumors that responded to ICIs and was associated with improved survival outcomes, outperforming CD3, CD8 and PD-L1. In conclusion, these results suggest that SH2D1A provides information beyond established immune infiltration- and exhaustion-related markers, supporting further investigation of its potential role in biomarker-guided prediction of ICI response in melanoma.

Urgent systemic chemotherapy (nanoparticle paclitaxel, carboplatin, 5-FU) was initiated, followed by addition of toripalimab...Early recognition and prompt initiation of chemo-immunotherapy can stabilize airway compromise and induce rapid response in tracheal SCC. However, aggressive biology mandates close follow-up and individualized, multidisciplinary management.

Single-cell transcriptional profiling was performed on immune cells in PD-L1-low Lewis lung carcinoma (LLC) treated with cyclophosphamide (CTX) and/or anti-PD-1 antibodies...PD-1 blockade synergizes with cytotoxic chemotherapy to diversify and expand PD-1 lineage-traced CTL clonotypes, driving robust antitumor immunity. Thus, our fate-mapping system is a valuable tool to search for immune cells responsive to ICI therapy.

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