Prognostic significance of soluble forms of immune checkpoint PD-1/PDL1 receptor and ligand in blood plasma of gastric cancer patients

Abstract

Analysis of long-term treatment results of 101 primary gastric cancer patients at various stages of the tumor process followed during 1 - 41 months (median - 6,4 months) from the onset of specific treatment are presented depending on the levels of soluble forms (s) of PD-1 receptor and its ligand PD-L1 in blood plasma. Overall survival assessed by Kaplan-Meyer analysis and with the help of Cox multiparametric regression model was applied as the criterion of prognostic value. It was found that at high (≥ 35 pg/ml) sPD-L1 levels in blood plasma, the overall survival of patients with gastric cancer was statistically significantly lower than at the marker’s levels below 35 pg / ml (p <0.045): 1-year survival comprised 78 and 96%, 2-year - 52 and 78%; 3-year - 40 and 61% at high and low sPD-L1 respectively. Median survival of patients with high plasma sPD-L1 comprised 29 months, of those with low sPD-L1 was not achieved during the whole follow-up period. This trend was observed not only in the total group of stage I-IV gastric cancer patients, but also in patients at the early stages of the disease, though sPD-L1 did not show an independent prognostic value in multiparametric model. At the same time, the overall survival of patients with gastric cancer did not depend on the baseline levels sPD-1 in blood plasma. Thus, soluble ligand sPD-L1 can be considered as a potentially valuable factor for prognosis of gastric cancer patients’ survival, and, probably, of anti-PD-1/PD-L1 treatment efficiency, but further studies and patients’ monitoring are required to prove this statement.

Soluble Programmed Death Ligand-1 (sPD-L1): A Pool of Circulating Proteins Implicated in Health and Diseases

“…In most cases, the level of circulating sPD-L1 was found to be enhanced in the plasma of patients with the indicated pathology compared to healthy control (see Table 1 . For the oncology indications, the presence of sPD-L1 and its significance are discussed in the following studies: AEC [ 41 ]; BTC [ 42 , 43 ]; brain tumors [ 26 , 44 ]; CRCC [ 45 , 46 ]; CRC [ 47 ]; cutaneous melanoma [ 48 ]; DLBCL [ 49 , 50 ]; EOC [ 51 , 52 ]; ENKTL [ 53 , 54 ]; HNSCC [ 36 ]; HCC [ 55 , 56 , 57 ]; HL [ 54 , 58 ]; mesothelioma [ 59 , 60 ]; NC [ 61 , 62 ]; PGC [ 63 , 64 , 65 ]; NSCLC [ 66 , 67 ]; PC [ 68 ]; PCNSL [ 50 ]; STS [ 69 , 70 ]; TC [ 71 ]; TNBC [ 72 ]; WM [ 73 ].…”

“…At the same time, a high level of soluble PD-L1 in peripheral blood often predicts poor prognosis in patients with solid tumors [ 111 ]. However, as an isolated marker, it cannot be considered a predictor of overall survival of patients with solid tumors [ 63 ]. The level of sPD-L1 does not always correlate with response to immune-sensitivity, notably in lung cancers [ 45 , 66 ].…”

Transforming growth factor-β1 and soluble co-inhibitory immune checkpoints as putative drivers of immune suppression in patients with basal cell carcinoma

“…These co-inhibitory ICPs are expressed on various cell types in the tumor microenvironment (TME), including immune suppressor cells of the adaptive and innate immune systems, as well as tumor cells per se and cancer-associated fibroblasts, among others [12] , [13] , [14] . In addition, co-inhibitory soluble ICPs (sICPs) have also been detected in the systemic circulation of cancer patients with various types of advanced malignancies, including, but not limited to, melanoma and cancers of the breast, esophagus, head and neck, lung and stomach [15] , [16] , [17] , [18] , [19] , [20] .…”

Levels of Circulating PD-L1 Are Decreased in Patients with Resectable Cholangiocarcinoma

“…Moreover, in a series of papers, different authors recently suggested a role of sPD-L1 as a biomarker in very different cancer entities and have suggested a diagnostic, prognostic and predictive role of this molecular marker in cancers originating from the urothelium, lung and brain [ 12 , 13 , 14 ]. In addition, sPD-L1 was found to be a prognostic marker in gastrointestinal stromal cancers and gastric cancers [ 15 , 16 ]. Therefore, evaluation of PD-L1 expression and/or PD-L1 serum levels as a surrogate for PD-L1 expression has been proposed as a valuable tool for the estimation of patients’ prognosis in manifold cancers.…”