PD-L1 negative

APOBEC mutational signatures represent a robust predictive biomarker for ICI response in TMB-low metastatic NSCLC, identifying responders particularly among PD-L1-negative patients where biomarker guidance is most needed, detectable from targeted gene panels used in routine clinical practice.

P1/2, N=51, Completed, National Cancer Institute (NCI) | Active, not recruiting --> Completed

Within the PD-L1-positive/HLA-G-negative subgroup, high CD8 density was independently associated with improved DFS but not OS. Integrating HLA-G with PD-L1 and CD8 assessment may refine prognostic stratification and help identify patients who could benefit from HLA-G-targeted strategies, alone or in combination with PD-1/PD-L1 blockade.

Immunotherapy-related pneumonitis ≥grade 1 was documented in 15.7% patients. In real-world practice, durvalumab improves OS and PFS in PD-L1-positive unresectable stage III NSCLC and its omission appears particularly unfavourable.

These findings suggest that iSBRT + anti-PD-L1 may convert immune-cold ER+HER2- BC into more inflamed tumors and improve response, particularly in PD-L1-negative disease. ClinicalTrials.gov registration: NCT03875573 .

The incidence of grade 3-4 adverse events (AEs) was similar in three groups. Among the first-line treatment regimens for metastatic lung adenocarcinoma patients with negative or low PD-L1 expression, PD-1/PD-L1 inhibitors plus anti-angiogenic agents with chemotherapy showed significant benefit in PFS compared to anti-angiogenic agents plus chemotherapy and PD-1/PD-L1 inhibitors plus chemotherapy.

Importantly, findings from the clinical cohort confirmed that ITGA3 expression was positively correlated with CD206 and PD-L1, and negatively correlated with CD8 and CD19, supporting its role in shaping an immunosuppressive microenvironment. ITGA3 is a promising immune-related biomarker for predicting prognosis and therapeutic response in PDAC and may provide a potential target for personalized treatment strategies.

The TMEp phase integrated stereotactic body radiotherapy (SBRT), low-dose etoposide, and anlotinib, followed by CI with the programmed death 1 (PD-1)/cytotoxic T lymphocyte antigen 4 (CTLA-4) bispecific antibody cadonilimab and concurrent probiotic supplementation...The TMEp-CI-M platform may enhance the efficacy of immunotherapy in ES-SCLC, enabling durable responses even in patients with brainstem metastases. Although this platform has demonstrated promise across multiple tumor types, further prospective and mechanistic studies are warranted to confirm its clinical utility.

P1, N=30, Recruiting, University of Texas Southwestern Medical Center | Trial completion date: Apr 2026 --> Apr 2029 | Trial primary completion date: Apr 2026 --> Apr 2028

ARID1A IHC is a reliable tool to identify these aggressive tumors. Associated PD-L1 expression may offer new therapeutic options via checkpoint inhibitors.

The predominance of PD-L1 negativity together with MSS/low-TMB features suggests a generally immunologically "cold" phenotype in most reported tumors, while exploratory fusion partner-specific enrichment patterns may help refine diagnostic suspicion and generate hypotheses for future biomarker-guided stratification. These findings provide a translational basis for rare-cancer immunobiology research and for the rational design of biomarker-integrated prospective studies.

In cisplatin-ineligible populations, ICI regimens did not improve PFS compared with cetuximab plus RT. This study showed that although in the overall population there was no significant difference in EFS/PFS/DFS, in the PD-L1-positive subgroup, patients experienced significantly improved PFS with ICIs compared with control, while in the PD-L1-negative subgroup, patients demonstrated inferior PFS in the ICIs arm; these results were mirrored in the cisplatin-eligible subgroup.