(Open access funding provided by Semmelweis University)
Immune checkpoint inhibitors (ICI) such as anti-PD-L1 and anti-PD-1 agents have been
proven to be effective in various cancers. However, the rate of non-responders is
still high in all cancer entities. Therefore, the identification of biomarkers that
could help to optimize therapeutic decision-making is of great clinical importance.
Soluble PD-L1 (sPD-L1) and PD-1 (sPD-1) are emerging blood-based biomarkers and were
previously shown to be prognostic in various clinical studies.We aimed to evaluate
the prognostic relevance of sPD-L1 and sPD-1 in patients with different tumor entities
who underwent ICI therapy.We searched for articles in PubMed via Medline, Embase,
Scopus, and Cochrane databases. The primary outcome was overall survival (OS) and
progression-free survival (PFS); furthermore, we analyzed on-treatment serum level
changes of sPD-L1 and sPD-1 during ICI therapy.We synthesized the data of 1,054 patients
with different cancer types from 15 articles. Pooled univariate analysis showed that
elevated levels of sPD-L1 were significantly associated with inferior OS (HR = 1.67;
CI:1.26-2.23, I2 = 79%, p < 0.001). The strongest association was found in non-small
cell lung cancer, whereas weaker or no association was observed in melanoma as well
as in renal cell and esophageal cancers. Pooled multivariate analysis also showed
that elevated levels of sPD-L1 correlated with worse OS (HR = 1.62; CI: 1.00-2.62,
I2 = 84%, p = 0.05) and PFS (HR = 1.71; CI:1.00-2.94, I2 = 82%, p = 0.051). Furthermore,
we observed that one or three months of anti-PD-L1 treatment caused a strong (27.67-fold)
elevation of sPD-L1 levels in malignant mesothelioma and urothelial cancer.We found
significantly inferior OS in ICI-treated cancer patients with elevated pre-treatment
sPD-L1 levels, but this association seems to be tumor type dependent. In addition,
sPD-L1 increases during anti-PD-L1 therapy seems to be therapy specific.
