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Updated: Jun 21, 2026
Quantitative Mass Spectrometric Profiling of Cancer-cell Proteomes Derived From Liquid and Solid Tumors
Published on: February 27, 2015
Programmed Cell Death Ligand as a Biomarker for Response to Immunotherapy: Contribution of Mass Spectrometry-Based
Marco Agostini1, Pietro Traldi1, Mahmoud Hamdan1
1Istituto di Ricerca Pediatrica Città della Speranza, Corso Stati Uniti 4, 35100 Padova, Italy.
Abstract:
Immune checkpoint inhibition is a major component in today's cancer immunotherapy. In recent years, the FDA has approved a number of immune checkpoint inhibitors (ICIs) for the treatment of melanoma, non-small-cell lung, breast and gastrointestinal cancers. These inhibitors, which target cytotoxic T-lymphocyte antigen-4, programmed cell death (PD-1), and programmed cell death ligand (PD-L1) checkpoints have assumed a leading role in immunotherapy. The same inhibitors exert significant antitumor effects by overcoming tumor cell immune evasion and reversing T-cell exhaustion. The initial impact of this therapy in cancer treatment was justly described as revolutionary, however, clinical as well as research data which followed demonstrated that these innovative drugs are costly, are associated with potentially severe adverse effects, and only benefit a small subset of patients. These limitations encouraged enhanced research and clinical efforts to identify predictive biomarkers to stratify patients who are most likely to benefit from this form of therapy. The discovery and characterization of this class of biomarkers is pivotal in guiding individualized treatment against various forms of cancer. Currently, there are three FDA-approved predictive biomarkers, however, none of which on its own can deliver a reliable and precise response to immune therapy. Present literature identifies the absence of precise predictive biomarkers and poor understanding of the mechanisms behind tumor resistance as the main obstacles facing ICIs immunotherapy. In the present text, we discuss the dual role of PD-L1 as a biomarker for response to immunotherapy and as an immune checkpoint. The contribution of mass spectrometry-based analysis, particularly the impact of protein post-translational modifications on the performance of this protein is underlined.
Insights
Immune checkpoint inhibitors (ICIs) show promise in cancer treatment but have limitations. Research is focusing on programmed cell death ligand-1 (PD-L1) as a biomarker to predict patient response to immunotherapy.
Area of Science:
- Oncology
- Immunology
- Biochemistry
Background:
- Immune checkpoint inhibitors (ICIs) are revolutionizing cancer therapy, targeting pathways like PD-1/PD-L1.
- Despite efficacy, ICIs face challenges including cost, side effects, and limited patient benefit.
- Identifying predictive biomarkers is crucial for stratifying patients and optimizing ICI therapy.
Purpose of the Study:
- To explore the dual role of programmed cell death ligand-1 (PD-L1) in immunotherapy response.
- To highlight the importance of PD-L1 as both an immune checkpoint and a predictive biomarker.
- To emphasize the contribution of mass spectrometry in understanding PD-L1's function.
Main Methods:
- Review of current literature on immune checkpoint inhibitors and biomarkers.
- Discussion of PD-L1's function as an immune checkpoint.
- Exploration of mass spectrometry-based analysis for PD-L1 characterization.
Main Results:
- PD-L1 plays a critical role in tumor immune evasion and T-cell exhaustion.
- Current FDA-approved biomarkers for ICI therapy lack precision.
- Mass spectrometry can reveal post-translational modifications of PD-L1, impacting its performance.
Conclusions:
- PD-L1 holds significant potential as a predictive biomarker for ICI therapy.
- Further research into PD-L1, including its post-translational modifications, is essential for improving cancer treatment outcomes.
- Understanding PD-L1 mechanisms is key to overcoming resistance to immunotherapy.
