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2018 ; 9
(ä): 1474
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Biomarkers for Clinical Benefit of Immune Checkpoint Inhibitor Treatment-A Review
From the Melanoma Perspective and Beyond
#MMPMID30002656
Buder-Bakhaya K
; Hassel JC
Front Immunol
2018[]; 9
(ä): 1474
PMID30002656
show ga
BACKGROUND: Immune checkpoint inhibition (ICI) with anti-CTLA-4 and/or anti-PD-1
antibodies is standard treatment for metastatic melanoma. Anti-PD-1
(pembrolizumab, nivolumab) and anti-PD-L1 antibodies (atezolizumab, durvalumab,
and avelumab) have been approved for treatment of several other advanced
malignancies, including non-small-cell lung cancer (NSCLC); renal cell, and
urothelial carcinoma; head and neck cancer; gastric, hepatocellular, and
Merkel-cell carcinoma; and classical Hodgkin lymphoma. In some of these
malignancies approval was based on the detection of biomarkers such as PD-L1
expression or high microsatellite instability. METHODS: We review the current
status of prognostic and predictive biomarkers used in ICI for melanoma and other
malignancies. We include clinical, tissue, blood, and stool biomarkers, as well
as imaging biomarkers. RESULTS: Several biomarkers have been studied in ICI for
metastatic melanoma. In clinical practice, pre-treatment tumor burden measured by
means of imaging and serum lactate dehydrogenase level is already being used to
estimate the likelihood of effective ICI treatment. In peripheral blood, the
number of different immune cell types, such as lymphocytes, neutrophils, and
eosinophils, as well as different soluble factors, have been correlated with
clinical outcome. For intra-tumoral biomarkers, expression of the PD-1 ligand
PD-L1 has been found to be of some predictive value for anti-PD-1-directed
therapy for NSCLC and melanoma. A high mutational load, particularly when
accompanied by neoantigens, seems to facilitate immune response and correlates
with patient survival for all entities treated by use of ICI. Tumor
microenvironment also seems to be of major importance. Interestingly, even the
gut microbiome has been found to correlate with response to ICI, most likely
through immuno-stimulatory effects of distinct bacteria. New imaging biomarkers,
e.g., for PET, and magnetic resonance imaging are also being investigated, and
results suggest they will make early prediction of patient response possible.
CONCLUSION: Several promising results are available regarding possible biomarkers
for response to ICI, which need to be validated in large clinical trials. A
better understanding of how ICI works will enable the development of biomarkers
that can predict the response of individual patients.