Aims: Programmed cell death ligand 1 (PD-L1) expression, used universally to predict response of non-small cell lung cancer (NSCLC) to immune-modulating drugs, is a fragile biomarker due to biological heterogeneity and challenges in interpretation. The aim of this study was to assess current PD-L1 testing practices in the UK, which may help to define strategies to improve its reliability and consistency.
Methods: A questionnaire covering NSCLC PD-L1 testing practice was devised and members of the Association of Pulmonary Pathologists were invited to complete this online.
Results: Of 44 pathologists identified as involved in PD-L1 testing, 32 (73%) responded. There was good consistency in practice and approach, but there was wide variability in the distribution of PD-L1 scoring. Although the proportions of scores falling into the three groups (negative, low and high) defined by the 1% and 50% 'cut-offs' (38%, 33% and 27%, respectively) reflect the general experience, the range within each group was wide at 23-70%, 10-60% and 15-36%, respectively.
Conclusions: There is inconsistency in the crucial endpoint of PD-L1 testing of NSCLC, the expression score that guides management. Addressing this requires formal networking of individuals and laboratories to devise a strategy for its reduction.
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http://dx.doi.org/10.1136/jcp-2022-208643 | DOI Listing |
Diagnostics (Basel)
January 2025
Department of Regulatory Science, College of Pharmacy, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea.
: Earlier detection of severe immune-related hematological adverse events (irHAEs) in cancer patients treated with a PD-1 or PD-L1 inhibitor is critical to improving treatment outcomes. The study aimed to develop a simple machine learning (ML) model for predicting irHAEs associated with PD-1/PD-L1 inhibitors. : We utilized the Observational Medical Outcomes Partnership-Common Data Model based on electronic medical records from a tertiary (KHMC) and a secondary (KHNMC) hospital in South Korea.
View Article and Find Full Text PDFCancer Chemother Pharmacol
January 2025
Department of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Background: The expression of anti-programmed cell death ligand-1 (PD-L1) in tumors is widely used as a biomarker to predict the therapeutic efficacy of anti-programmed cell death-1(PD-1)/PD-L1 antibodies. However, the predictive accuracy of this method is limited. High-mobility group box 1 (HMGB1) is known to modulate cancer immunity.
View Article and Find Full Text PDFCancer Immunol Res
January 2025
Genentech, United States.
Testing for PD-L1 expression by immunohistochemistry (IHC) is used to predict immune checkpoint blockade (ICB) benefit but has performed inconsistently in urothelial cancer (UC) clinical trials. Different approaches are used for PD-L1 IHC. We analyzed paired PD-L1 IHC data on UC samples using the SP142 and 22C3 assays from the phase 3 IMvigor130 trial and found discordant findings summarized by four phenotypes: PD-L1 positive by both assays (PD-L1 double positive; PD-L1DP), PD-L1 positive by the SP142 assay only (SP142 single positive; SP142SP), PD-L1 positive by the 22C3 assay only (22C3 single positive; 22C3SP), and PD-L1 negative by both assays double negative (PD-L1 double negative; PD-L1DN).
View Article and Find Full Text PDFCytokine
January 2025
Collegium Medicum, Jan Kochanowski University in Kielce, 25-317 Kielce, Poland; Department of Endocrinology, Holy Cross Cancer Center, 25-734 Kielce, Poland.
Background: CD4+ T lymphocytes are key immune cells involved in orbital inflammation in thyroid eye disease (TED). Inhibition of their activity is important in treatment of TED, but effective drugs targeting these cells are lacking. The programmed cell death-1/programmed cell death ligand-1 pathway has been implicated in several T-cell-mediated diseases.
View Article and Find Full Text PDFNeoplasma
December 2024
Department of Gastrointestinal Surgery, Renmin Hospital of Wuhan University, Wuchang, Wuhan, Hubei, China.
Many lines of evidence suggest that circular RNAs (circRNAs) are closely associated with the occurrence and progression of colon cancer. The objective of this study was to investigate the regulatory effects and mechanisms of circ_0075829 on ferroptosis and immune escape in colon cancer. We utilized colon cancer cell lines and a xenograft mouse model to analyze the function of circ_0075829 in vitro and in vivo.
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