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Biomarkers of response to PD-1/PD-L1 inhibition
Saman Maleki Vareki1, Carmen Garrigós2, Ignacio Duran2
1Cancer Research Laboratory Program, Lawson Health Research Institute, London, Ontario, Canada.
Abstract:
Immunotherapy is a promising treatment strategy for cancer that has recently shown unprecedented survival benefits in selected patients. A number of immunomodulatory agents that target immune system checkpoints such as the cytotoxic T-lymphocyte antigen 4 (CTLA-4), the programmed death-1 (PD-1) or its ligand (PD-L1), have received regulatory approval for the treatment of multiple cancers including malignant melanoma, non-small cell lung cancer, renal cell carcinoma, classical Hodgkin lymphoma, and recurrent or metastatic head and neck squamous cell carcinoma. Nevertheless, a substantial proportion of patients treated with checkpoint inhibitors have little or no benefit while these treatments are costly and might have associated toxicities. Hence, the establishment of valid predictors of treatment response has become a priority. This review summarizes the current evidence around biomarkers of response to PD-1/PD-L1 inhibition, considering features related to the tumor and to the host immune system.
Insights
Immunotherapy using checkpoint inhibitors shows promise for cancer, but not all patients benefit. This review explores biomarkers to predict response to programmed death-1 (PD-1)/PD-L1 therapies.
Area of Science:
- Oncology
- Immunology
Background:
- Immunotherapy, particularly checkpoint inhibitors targeting CTLA-4, PD-1, and PD-L1, offers significant survival benefits in various cancers.
- Approved for melanoma, lung, kidney, Hodgkin lymphoma, and head/neck cancers, these treatments are not universally effective.
- High costs and potential toxicities necessitate identifying patients likely to respond.
Purpose of the Study:
- To review current evidence on biomarkers predicting response to PD-1/PD-L1 inhibition.
- To analyze tumor- and host-related factors influencing treatment efficacy.
Main Methods:
- Literature review of studies on biomarkers for PD-1/PD-L1 inhibitors.
- Analysis of tumor characteristics (e.g., mutations, gene expression) and host immune factors (e.g., immune cell infiltration).
Main Results:
- Biomarkers related to tumor mutational burden and PD-L1 expression are emerging predictors.
- Host immune system features also play a crucial role in treatment response.
- No single biomarker is currently sufficient for predicting response across all patients.
Conclusions:
- Predictive biomarkers are essential for optimizing PD-1/PD-L1 immunotherapy.
- A combination of tumor and host factors may provide a more accurate prediction of treatment response.
- Further research is needed to validate and implement these biomarkers in clinical practice.
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