Among patients with a tumor proportion score for programmed death ligand 1 (PD-L1) of 50% or greater, pembrolizumab has replaced cytotoxic chemotherapy as the first-line treatment of choice.
Even in the event of failure of treatment with checkpoint inhibitors in the background of a case with a higher tumor mutational burden and PD-L1 positivity, targeting specific genomic alterations may still result in patient benefit.
High tumor mutation burden and strong PD-L1 staining may provide a rationale for the use of targeted immunotherapies in pulmonary sarcomatoid carcinomas.
Allele frequency-adjusted blood-based tumor mutational burden as a predictor of overall survival for non-small cell lung cancer patients treated with PD-1/PD-L1 inhibitors.
We collected retrospective data about patients with advanced non-small cell lung cancers, and synchronous tumor paired samples were analyzed for PD-L1 immunohistochemistry (IHC) and oncogene molecular statuses.
Positive PD-L1 expression (including TPS ≥50% and TPS <50%) in LUAD cohort was significantly associated with male sex (P=0.046), current/ever smoking history (P=0.002), mutation pan-negative status (P=0.038), solid-predominant subtype (P<0.001), large tumor size (P=0.027) and lymph node metastasis (P=0.019).
To depict the genomic landscape of Chinese early-stage lung squamous cell carcinoma (LUSC) and investigate its correlation with tumor mutation burden (TMB), PD-L1 expression, and immune infiltrates.
Checkpoint inhibitors targeted at programmed cell death-1 receptor (PD-1) and its ligand (PD-L1) can result in significant benefit to a small proportion of patients with cancer, including those with tumors of the stomach and gastroesophageal junction.
Secondary end points included evaluation of the ORR by platinum sensitivity, assessment of progression-free survival, assessment of safety data, and investigation of the association of tumorPD-L1 with response to therapy.
In particular, tumor-infiltrating immune cells, gene expression analysis, mismatch- repair deficiency, and tumor mutational landscape may play a central role in predicting clinical benefits of CTLA-4 and/or PD-1/PD-L1 checkpoint inhibitors.
In studies of unselected patient populations, it was shown that melanoma, non small cell lung cancer (NSCLC), renal cell carcinoma and urothelial carcinoma patients treated with CTLA-4, PD-1 or PD-L1 inhibitors had an improved objective response and overall survival relative to chemotherapy or historical trends, and several ICIs have been approved for the treatment of these and other indications.More recently, several groups found that response to ICI therapy strongly correlates with a high burden of single nucleotide variant (SNV) mutations in the tumor genome, termed tumor mutational burden (TMB), usually expressed as the number of nonsynonymous single nucleotide variants per megabase of sequenced genome.
In conclusion, the presence of enhanced immune infiltration, particularly high numbers of PD-1 and PD-L1 positive cells, in highly mutated, neoantigen-rich <i>POLE</i>-mutant and MSI endometrial tumors suggests sensitivity to immune checkpoint inhibitors.
Next generation sequencing of his metastatic liver tumor demonstrated a high tumor mutational burden (103 mutations per megabase) and the genomic amplification of <i>PD-L1</i>, both of which are features that predict response to anti-PD1/PD-L1 immunotherapy.
CTLA-4 TC intensity was significantly higher in yolk sac tumor, choriocarcinoma and teratoma, while PD-L1TC positivity was significantly more frequent in choriocarcinoma.
Programmed cell death protein 1 (PD-1) blockade provides a therapeutic opportunity for patients with high tumor mutation burden (TMB), high microsatellite instability (MSI-H), deficient mismatch repair (dMMR) and/or positive programmed cell death ligand 1 (PD-L1) expression.