Assays for predicting and monitoring responses to lung cancer immunotherapy
Cristina Teixidó1, Niki Karachaliou1, Maria González-Cao1
11 Pangaea Biotech, Quirón Dexeus University Hospital, Barcelona 08028, Spain ; 2 Dr. Rosell Oncology Institute, Quirón Dexeus University Hospital, Barcelona 08028, Spain ; 3 Cancer Biology and Precision Medicine Program, Catalan Institute of Oncology, Hospital Germans Trias i Pujol, Badalona 08916, Spain.
Abstract:
Immunotherapy has become a key strategy for cancer treatment, and two immune checkpoints, namely, programmed cell death 1 (PD-1) and its ligand (PD-L1), have recently emerged as important targets. The interaction blockade of PD-1 and PD-L1 demonstrated promising activity and antitumor efficacy in early phase clinical trials for advanced solid tumors such as non-small cell lung cancer (NSCLC). Many cell types in multiple tissues express PD-L1 as well as several tumor types, thereby suggesting that the ligand may play important roles in inhibiting immune responses throughout the body. Therefore, PD-L1 is a critical immunomodulating component within the lung microenvironment, but the correlation between PD-L1 expression and prognosis is controversial. More evidence is required to support the use of PD-L1 as a potential predictive biomarker. Clinical trials have measured PD-L1 in tumor tissues by immunohistochemistry (IHC) with different antibodies, but the assessment of PD-L1 is not yet standardized. Some commercial antibodies lack specificity and their reproducibility has not been fully evaluated. Further studies are required to clarify the optimal IHC assay as well as to predict and monitor the immune responses of the PD-1/PD-L1 pathway.
Insights
Programmed cell death 1 (PD-1) and its ligand (PD-L1) are key immunotherapy targets for cancer. While PD-L1 expression shows promise as a biomarker, its correlation with prognosis and standardized assessment remain controversial.
Area of Science:
- Oncology
- Immunology
- Biomarker Research
Background:
- Immunotherapy targeting immune checkpoints like programmed cell death 1 (PD-1) and its ligand (PD-L1) is a significant advancement in cancer treatment.
- Blocking the PD-1/PD-L1 interaction has shown efficacy in clinical trials for advanced solid tumors, including non-small cell lung cancer (NSCLC).
- PD-L1 is expressed by various cell types and tumors, indicating a role in modulating systemic immune responses and the lung microenvironment.
Purpose of the Study:
- To evaluate the role of PD-L1 as a predictive biomarker in cancer treatment.
- To investigate the controversial correlation between PD-L1 expression and patient prognosis.
- To address the need for standardized assessment of PD-L1 in clinical trials.
Main Methods:
- Review of early-phase clinical trials for advanced solid tumors, focusing on PD-1/PD-L1 blockade.
- Analysis of studies measuring PD-L1 expression in tumor tissues using immunohistochemistry (IHC).
- Evaluation of antibody specificity and reproducibility in PD-L1 assessment.
Main Results:
- The PD-1/PD-L1 blockade demonstrates promising antitumor activity in advanced cancers like NSCLC.
- The role of PD-L1 in prognosis remains controversial, requiring further investigation.
- Current IHC methods for PD-L1 assessment lack standardization, with variable antibody specificity and reproducibility.
Conclusions:
- PD-L1 is a critical immunomodulating factor, but its utility as a predictive biomarker needs more supporting evidence.
- Standardization of IHC assays is crucial for reliable PD-L1 assessment.
- Further research is necessary to optimize PD-L1 detection and its application in predicting and monitoring immune responses to PD-1/PD-L1 pathway inhibitors.
