Soluble PD‐1 and PD‐L1 as potential biomarkers for classical Hodgkin lymphoma

Silva, Priscilla Brito da; Real, Juliana Monte; Ferreira, Ludmila Rodrigues Pinto; Esteves, Gustavo H.; Brito, Fábio do Nascimento; Baiocchi, Otávio C.G.

doi:10.1002/hon.2542

Cited by 13 publications

(15 citation statements)

References 16 publications

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“…These results are consistent with the relationship between poor prognosis and high expression of PD-L1 in tumor cells [32,33]. Because overexpression of PD-L1 in tumor cells is related to the downregulation of effector T-cell function and represents a potent mechanism of tumor immune evasion [34], our findings imply a possible role for sPD-L1 in allowing tumor cells to escape from anti-tumor immunity, similar to the T-cell exhaustion through the immune checkpoint mechanism seen in the PD1/PD-L1 axis [35,36]. Thus, patients with elevated levels of sPD-L1 might be more likely to have surviving residual tumor cells after HD-MTX-containing chemotherapy.…”

Section: Discussionsupporting

confidence: 87%

Serum levels of soluble programmed death-ligand 1 (sPD-L1) in patients with primary central nervous system diffuse large B-cell lymphoma

et al. 2020

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Background: The interaction of programmed death-1 protein (PD-1) and programmed death-1 ligand (PD-L1) produces immunosuppressive activity, protecting tumor cells from anti-tumor immunity and possibly releasing soluble PD-L1 (sPD-L1) from PD-L1 expressing tumor cells. Therefore, we measured serum levels of sPD-L1 in patients with primary central nervous system lymphoma (PCNSL) and explored its clinical implications. Methods: Sixty-eight patients with newly diagnosed PCNSL had diffuse large B-cell lymphoma and were treated with high-dose methotrexate-containing chemotherapy. The measurement of sPD-L1 and cytokines was performed using serum samples archived at diagnosis, and the tissue expression of PD-L1 was also analyzed from archived paraffin-embedded tissue blocks. Disease relapse, progression-free survival (PFS), and overall survival (OS) were analyzed according to the extent of sPD-L1 in serum and PD-L1 in tissue. Results: The median level of serum sPD-L1 (0.429 ng/mL) was higher than in healthy control patients (0.364 ng/mL). The occurrence of relapse was more frequent in the high sPD-L1 (78%) than the low sPD-L1 group (50%), though the groups did not have different clinical or pathological characteristics at diagnosis. As a result, the OS and PFS for the high sPD-L1 group were significantly lower than those in the low group. PD-L1-positive tumor cells were found in 35 patients (67%), and the extent of PD-L1-postive tumor cells was positively associated with serum sPD-L1 levels (r = 0.299, P = 0.031). Among the 34 cytokines analyzed, only the serum level of IL-7 correlated with the serum level of sPD-L1 (r = 0.521, P < 0.001). Conclusions: Serum levels of sPD-L1 could reflect the expression of PD-L1 in PCNSL tumor cells and predict patient survival outcomes. Therefore, sPD-L1 in serum could be a feasible biomarker for determining a risk-adapted treatment strategy for PCNSL patients.

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Section: Discussionsupporting

confidence: 87%

Serum levels of soluble programmed death-ligand 1 (sPD-L1) in patients with primary central nervous system diffuse large B-cell lymphoma

et al. 2020

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“…These results are consistent with the relationship between poor prognosis and high expression of PD-L1 in tumor cells [32,33]. Because overexpression of PD-L1 in tumor cells is related to the downregulation of effector T-cell function and represents a potent mechanism of tumor immune evasion [34], our findings imply a possible role for sPD-L1 in allowing tumor cells to escape from anti-tumor immunity, similar to the Tcell exhaustion through the immune checkpoint mechanism seen in the PD1/PD-L1 axis [35,36] Figure 2C). In line with those findings, the survival analysis showed a trend of better OS in patients with low PD-L1 expression compared to high PD-L1 (P = 0.130, Figure 2E), and the extent of PD-L1 expression in immune cells showed no difference between low and high groups (P = 0.984, Figure 2F).…”

Section: Discussionsupporting

confidence: 87%

Serum levels of soluble programmed death-ligand 1 (sPD-L1) in patients with primary central nervous system diffuse large B-cell lymphoma

Cho

Lee

Yoon

et al. 2020

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Background The interaction of programmed death-1 protein (PD-1) and programmed death-1 ligand (PD-L1) produces immunosuppressive activity, protecting tumor cells from anti-tumor immunity and possibly releasing soluble PD-L1 (sPD-L1) from PD-L1 expressing tumor cells. Therefore, we measured serum levels of sPD-L1 in patients with primary central nervous system lymphoma (PCNSL) and explored its clinical implications. Methods Sixty-eight patients with newly diagnosed PCNSL had diffuse large B-cell lymphoma and were treated with high-dose methotrexate-containing chemotherapy. The measurement of sPD-L1 and cytokines was performed using serum samples archived at diagnosis, and the tissue expression of PD-L1 was also analyzed from archived paraffin-embedded tissue blocks. Disease relapse, progression-free survival (PFS), and overall survival (OS) were analyzed according to the extent of sPD-L1 in serum and PD-L1 in tissue. Results The median level of serum sPD-L1 (0.429 ng/mL) was higher than in healthy control patients (0.364 ng/mL). The occurrence of relapse was more frequent in the high sPD-L1 (78%) than the low sPD-L1 group (50%), though the groups did not have different clinical or pathological characteristics at diagnosis. As a result, the OS and PFS for the high sPD-L1 group were significantly lower than those in the low group. PD-L1-positive tumor cells were found in 35 patients (67%), and the extent of PD-L1-postive tumor cells was positively associated with serum sPD-L1 levels ( r = 0.299, P = 0.031). Among the 34 cytokines analyzed, only the serum level of IL-7 correlated with the serum level of sPD-L1 (r = 0.521, P < 0.001). Conclusions Serum levels of sPD-L1 could reflect the expression of PD-L1 in PCNSL tumor cells and predict patient survival outcomes. Therefore, sPD-L1 in serum could be a feasible biomarker for determining a risk-adapted treatment strategy for PCNSL patients.

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“…Patients exhibited very good response to chemotherapy and radiotherapy, with only about 8% relapsing before 12 months after the end of therapy. Only patients with complete remission showed significant reduction of the sPD‐L1 levels, suggestive of a reprogramming of the immune system in the event of a positive response to the treatment . In NSCLC, one of the therapeutic strategies is to use epidermal growth factor receptor (EGFR)–tyrosine kinase inhibitors like erlotinib.…”

Section: Immune Checkpoint Molecules: Regulating the Immune Response mentioning

confidence: 99%

“…Only patients with complete remission showed significant reduction of the sPD-L1 levels, suggestive of a reprogramming of the immune system in the event of a positive response to the treatment. 110 In NSCLC, one of the therapeutic strategies is to use epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors like erlotinib. Preclinical data show that erlotinib affects the immune interaction in the tumor microenvironment 111 and the upregulation of the PD-1:PD-L1 pathway led to resistance to this therapy.…”

Section: Spd-1 In Cancer Prognosismentioning

confidence: 99%

“…45 sPD-1 Elevated levels in the sera-found in autoimmune diseases 106 ; correlates to cancer progression; correlates with sustained high hepatitis B viral load and increased risk of hepatocellular carcinoma 109 ; found in classical Hodgkin lymphoma (CHL). 110 sPD-L1 Elevated in the sera of renal cell carcinoma (RCC), 100 myeloma, 101 and B-cell lymphoma patients 102 and can be used as a prognostic marker.…”

Section: Tnf Superfamily Members In Tumor-specific Immune Response mentioning

confidence: 99%

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Soluble immune checkpoint molecules: Serum markers for cancer diagnosis and prognosis

2019

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Background With the recent advances in the understanding of the interaction of the immune system with developing tumor, it has become imperative to consider the immunological parameters for both cancer diagnosis and disease prognosis. Additionally, in the era of emerging immunotherapeutic strategies in cancer, it is very important to follow the treatment outcome and also to predict the correct immunotherapeutic strategy in individual patients. There being enormous heterogeneity among tumors at different sites or between primary and metastatic tumors in the same individual, or interpatient heterogeneity, it is very important to study the tumor‐immune interaction in the tumor microenvironment and beyond. Importantly, molecular tools and markers identified for such studies must be suitable for monitoring in a noninvasive manner. Recent findings Recent studies have shown that the immune checkpoint molecules play a key role in the development and progression of tumors. In‐depth studies of these molecules have led to the development of most of the cancer immunotherapeutic reagents that are currently either in clinical use or under different phases of clinical trials. Interestingly, many of these cell surface molecules undergo alternative splicing to produce soluble isoforms, which can be tracked in the serum of patients. Conclusions Several studies demonstrate that the serum levels of these soluble isoforms could be used as noninvasive markers for cancer diagnosis and disease prognosis or to predict patient response to specific therapeutic strategies.

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Soluble PD‐1 and PD‐L1 as potential biomarkers for classical Hodgkin lymphoma

Cited by 13 publications

References 16 publications

Serum levels of soluble programmed death-ligand 1 (sPD-L1) in patients with primary central nervous system diffuse large B-cell lymphoma

Serum levels of soluble programmed death-ligand 1 (sPD-L1) in patients with primary central nervous system diffuse large B-cell lymphoma

Serum levels of soluble programmed death-ligand 1 (sPD-L1) in patients with primary central nervous system diffuse large B-cell lymphoma

Soluble immune checkpoint molecules: Serum markers for cancer diagnosis and prognosis

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