High Serum Level of Soluble Programmed Death Ligand 1 is Associated With a Poor Prognosis in Hodgkin Lymphoma

Guo, Xin; Wang, Juan; Jin, Jietian; Chen, Hao; Zhen, Zijun; Jiang, Wenqi; Lin, Tongyu; Huang, Huiqiang; Xia, Zhong‐Jun; Sun, Xiaofei

doi:10.1016/j.tranon.2018.03.012

Cited by 24 publications

(27 citation statements)

References 60 publications

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“…We indeed found significant positive correlations between serum and peritoneal concentrations of sCTLA‐4 (r = 0.377, P = .002), sPD‐L1 (r = 0.306, P = .013), sHLA‐G (r = 0.406, P = .001), but not in sPD‐1 (r = 0.110, P = .384). Moreover, the significantly raised levels of local immune checkpoint molecules in the peritoneum could be due to the production by the ectopic lesions during chronic disease progression, as previously reported for sHLA‐G in endometriosis 17 and sPD‐L1 in Hodgkin lymphoma cases 24 . Their increased levels in the local tissue might be due to expression by endometrial lesions and local immune cells.…”

Section: Resultssupporting

confidence: 57%

Soluble immune checkpoints CTLA‐4, HLA‐G, PD‐1, and PD‐L1 are associated with endometriosis‐related infertility

Santoso

Sa’adi

Dwiningsih

et al. 2020

American J Rep Immunol

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Problem: Soluble immune checkpoint molecules constitute the emerging novel mediators in immune regulation. Their role in the pathogenesis of endometriosis has not been fully addressed. In this study, we aimed to investigate the relationship between the clinical manifestation of endometriosis-associated infertility and the level of four soluble immune checkpoints: sCTLA4, sHLA-G, sPD-1, and sPD-L1. Method of study: The soluble immune checkpoint concentrations in serum and peritoneal fluid from 88 patients who underwent laparoscopy were evaluated by the enzyme-linked immunosorbent assay (ELISA). Clinical and hematological parameters were documented and analyzed. Results: Endometriosis cases were evident to have significantly higher levels of serum sPD-L1 and all four molecules in peritoneal fluid compared to non-endometriosis control. Contrary, no significant differences were found in the concentration of serum sCTLA-4, sHLA-G and, sPD-1 between endometriosis and control group. There were significant positive correlations between serum and peritoneal fluid concentrations of sCTLA-4, sPD-L1, and sHLA-G. Serum sPD-L1 could discriminate endometriosis-related infertility to other pathological control. At a cutoff of 14,61 pg/ mL, serum sPD-L1 had a sensitivity of 77% and specificity of 83%. Moreover, sPD-L1 level showed positive correlations with pelvic adhesion score and myeloid cell count. Conclusion: The elevated level of sPD-L1 in serum and immune checkpoint molecules in the peritoneal fluid could represent the hallmark of immune regulation in endometriosis. Serum sPD-L1 could serve as a potential noninvasive endometriosis biomarker. Also, the immune compartment related to the local immune checkpoint molecules may be implicated in biological mechanisms underlying endometriosisrelated infertility.

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Section: Resultssupporting

confidence: 57%

Soluble immune checkpoints CTLA‐4, HLA‐G, PD‐1, and PD‐L1 are associated with endometriosis‐related infertility

Santoso

Sa’adi

Dwiningsih

et al. 2020

American J Rep Immunol

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“…In patients with oral squamous cell carcinoma, the increased expression of sPD-L1 has also been found to be associated with poor prognosis [ 41 ]. Similarly, in HL (Hodgkin Lymphoma), sPD-L1 levels are positively correlated with clinical stage [ 42 ]. However, the phenomenon in advanced gastric cancer seemed to be contradictory to the above researches, in which adenocarcinoma patients with higher PD-L1 expression had much better prognosis and less lymph node metastasis than low-expression patients [ 43 ].…”

Section: Spd-l1mentioning

confidence: 99%

Soluble immune checkpoints in cancer: production, function and biological significance

Yang

et al. 2018

j. immunotherapy cancer

206

199

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Immune checkpoints play important roles in immune regulation, and blocking immune checkpoints on the cell membrane is a promising strategy in the treatment of cancer. Based on this, monoclonal antibodies are having much rapid development, such as those against CTLA-4 (cytotoxic T lymphocyte antigen 4) and PD-1 (programmed cell death protein 1).But the cost of preparation of monoclonal antibodies is too high and the therapeutic effect is still under restrictions. Recently, a series of soluble immune checkpoints have been found such as sCTLA-4 (soluble CTLA-4) and sPD-1 (soluble PD-1). They are functional parts of membrane immune checkpoints produced in different ways and can be secreted by immune cells. Moreover, these soluble checkpoints can diffuse in the serum. Much evidence has demonstrated that these soluble checkpoints are involved in positive or negative immune regulation and that changes in their plasma levels affect the development, prognosis and treatment of cancer. Since they are endogenous molecules, they will not induce immunological rejection in human beings, which might make up for the deficiencies of monoclonal antibodies and enhance the utility value of these molecules. Therefore, there is an increasing need for investigating novel soluble checkpoints and their functions, and it is promising to develop relevant therapies in the future. In this review, we describe the production mechanisms and functions of various soluble immune checkpoint receptors and ligands and discuss their biological significance in regard to biomarkers, potential candidate drugs, therapeutic targets, and other topics.

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“…12,14,17 Moreover, the soluble forms of these factors have been associated with shorter outcome in many types of solid tumors such as digestive solid tumors and lung cancer. 16,18,19 However, the association between shorter outcome and high level of sPD-1 and sPD-L1 has been poorly investigated in patients with pancreatic adenocarcinoma. In order to correlate the levels of soluble forms of all immune checkpoints investigated in this study with overall patient's survival, we first used the linear Pearson correlation model.…”

Section: Pdac Patientsmentioning

confidence: 99%

Prognostic significance of circulating PD-1, PD-L1, pan-BTN3As, BTN3A1 and BTLA in patients with pancreatic adenocarcinoma

et al. 2019

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PDAC is one of the most heterogeneous cancers with low chemotherapeutic sensitivity due to a dense stroma, a weak vasculature and significant biological aggressivity. In cancer, suppressive immune checkpoints are often hyper-activated to ensure an effective evasion of tumor cells from immune surveillance. These immune checkpoints include in part, the B7/butyrophilin-like receptors such as butyrophilin sub-family 3A/CD277 receptors (BTN3A), the B and T lymphocyte attenuator (BTLA) belonging to the B7-like receptors and the programmed death protein (PD-1) with its ligand PD-L1. We evaluated the plasma level of these markers in 32 PDAC patients (learning cohort) by ad hoc developed ELISA's and showed that there are highly correlated. We used ROC curves and univariate analysis to characterize their prognostic relevance in these patients and showed that their plasma level can serve as survival predictor. Plasma level thresholds that correlate with less than six months survival were established for sPD-1 (>8.6 ng/ml), sPD-L1 (>0.36 ng/ml), sBTLA (>1.91 ng/ml), sBTN3A1 (>6.98 ng/ml) and pan-sBTN3A (>6.92 ng/ml). These thresholds were applied in independent validation cohort composed by 27 new samples and could efficiently discriminate short versus long PDAC survivors. Our study reveals that monitoring the concentration of soluble forms of inhibitory immune checkpoints in plasma can help predict survival in PDAC patients and therefore improve their treatments.

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High Serum Level of Soluble Programmed Death Ligand 1 is Associated With a Poor Prognosis in Hodgkin Lymphoma

Cited by 24 publications

References 60 publications

Soluble immune checkpoints CTLA‐4, HLA‐G, PD‐1, and PD‐L1 are associated with endometriosis‐related infertility

Soluble immune checkpoints CTLA‐4, HLA‐G, PD‐1, and PD‐L1 are associated with endometriosis‐related infertility

Soluble immune checkpoints in cancer: production, function and biological significance

Prognostic significance of circulating PD-1, PD-L1, pan-BTN3As, BTN3A1 and BTLA in patients with pancreatic adenocarcinoma

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