Charissa A. C. Jessurun, Julien A. M. Vos, Jacqueline Limpens, Rosalie M. Luiten
Abstract
Immune checkpoint inhibitors (ICIs), targeting CTLA-4 or PD-1 molecules, have shown impressive therapeutic results. However, only 20-40% of advanced melanoma patients have durable responses to ICI, and these positive effects must be balanced against severe off-target immune toxicity and high costs. This urges the development of predictive biomarkers for ICI response to select patients with likely clinical benefit from treatment. Although many candidate biomarkers exist, a systematic overview of biomarkers and their usefulness is lacking.
Here, we systematically review the current literature of clinical data of ICI treatment to provide an overview of candidate predictive biomarkers for ICI in melanoma patients.
To identify studies on biomarkers for clinical response or survival to ICI therapy in melanoma patients, we performed a systematic search in OVID MEDLINE and retrieved 429 publications, of which 67 met the eligibility criteria.
Blood and genomic biomarkers were mainly studied for CTLA-4 ICI, while tumor tissue markers were analyzed for both CTLA-4 and PD-1 ICI. Blood cytology and soluble factors correlated more frequently to overall survival (OS) than to response, indicating their prognostic rather than predictive nature. Systemic T-cell response and regulation markers correlated to response, but progression-free survival or OS were not analyzed. Tumor tissue analyses revealed response correlations with mutational load, neoantigen load, immune-related gene expression, and CD8+ T-cell infiltration at the invasive margin. The predictive value of PD-L1 varied, possibly due to the influence of T-cell infiltration on tumor PD-L1 expression. Genomic biomarker studies addressed CTLA-4 and other immune-related genes.
This review outlines all published biomarkers for ICI therapy and highlights potential candidate markers for future research. To date, PD-L1 is the best studied biomarker for PD-1 ICI response. The most promising candidate predictive biomarkers for ICI response have not yet been identified. Variations in outcome parameters, statistical power, and analyses hampered summary of the results. Further investigation of biomarkers in larger patient cohorts using standardized objectives and outcome measures is recommended.
Pharmacology, Toxicology and Pharmaceutical Science
3
3%
Other
11
11%
Unknown
30
31%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 4. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 17 October 2019.
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#8,264,793
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Outputs from Frontiers in oncology
#3,073
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Outputs of similar age
#122,402
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Outputs of similar age from Frontiers in oncology
#28
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Altmetric has tracked 25,382,440 research outputs across all sources so far. This one has received more attention than most of these and is in the 66th percentile.
So far Altmetric has tracked 22,428 research outputs from this source. They receive a mean Attention Score of 3.0. This one has done well, scoring higher than 85% of its peers.
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We're also able to compare this research output to 96 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 67% of its contemporaries.
