PD-L1 Expression in Sarcomas: An Immunohistochemical Study

2020 ◽  
Vol 154 (Supplement_1) ◽  
pp. S48-S49
Author(s):  
C Cunningham ◽  
J Schnabel ◽  
M Esebua ◽  
L Layfield
Keyword(s):  
T Lymphocytes ◽  
Metastatic Melanoma ◽  
Tumor Cells ◽  
Immunohistochemical Study ◽  
Membrane Staining ◽  
Programmed Death ◽  
Programmed Death 1

Abstract Introduction/Objective Immunotherapy is increasingly used for the treatment of metastatic melanoma and carcinomas. PD-I (programmed death 1) and its associated ligand (PD-L1) inhibits the activation of T lymphocytes. This inhibition can be impacted by a number of drugs. Response to these drugs is predicted by assessment of PD-L1 expression. PD-L1 expression varies between 19% and 92% in melanomas and carcinomas. PD-L1 expression is less well documented for sarcomas. Methods Fifty-one sarcomas of various histopathologic types were immunohistochemically stained (IHC) for PD-L1 using the antibody clone SP263 (Ventana, Tuscan, AZ). Membrane staining of tumor cells was quantitated as a percentage of total tumor cells. Sarcomas were judged as non-expressors (less than 1%) low-expressors (1 to 50%) and high expressors (greater than 50%). The percentage of each type of sarcoma judged as an expressor was determined. Results The percentage of each type of sarcoma expressing PD-L1 is reported and 20% of sarcomas expressed PD- L1. The percentage of sarcomas expressing PD-L1 varied significantly between types but the majority of sarcomas were non-expressors. Conclusion PD-L1 IHC expression is valuable in predicting response to immune-modulating drugs. Such therapies may be useful for treatment of metastatic sarcomas. Expression of PD-L1 in carcinomas and melanomas is variable ranging from 19% to 92%. In our study, a minority (20%) of sarcomas expressed PD-L1. Other studies have shown similar results with between 1.4 and 59% (average 24%) of sarcomas expressing PD-L1. Expression appears to be type specific. These finding suggest that PD-L1 based therapy may be less useful in sarcomas than in other malignancies.

Corrigendum to ‘High-affinity human programmed death-1 ligand-1 variant promotes redirected T cells to kill tumor cells’ [Cancer Lett. 447 (2019) 164–173]

2019 ◽  
Vol 452 ◽  
pp. 268-269
Author(s):  
Zhaoduan Liang ◽  
Yanyan Li ◽  
Ye Tian ◽  
Huanling Zhang ◽  
Wenxuan Cai ◽  
...  
Keyword(s):  
T Cells ◽  
Tumor Cells ◽  
High Affinity ◽  
Programmed Death ◽  
Programmed Death 1

High-affinity human programmed death-1 ligand-1 variant promotes redirected T cells to kill tumor cells

2019 ◽  
Vol 447 ◽  
pp. 164-173 ◽  
Author(s):  
Zhaoduan Liang ◽  
Yanyan Li ◽  
Ye Tian ◽  
Huanling Zhang ◽  
Wenxuan Cai ◽  
...  
Keyword(s):  
T Cells ◽  
Tumor Cells ◽  
High Affinity ◽  
Programmed Death ◽  
Programmed Death 1

scholarly journals High Expression of Pd-1 in Circulating Cells of Patients With Advanced Colorectal Cancer Receiving Adjuvant Therapy

2020 ◽  
Vol 19 ◽  
pp. 153303382096944
Author(s):  
Muhammed A. Bakhrebah ◽  
Mohammad Nasrullah ◽  
Wesam H. Abdulaal ◽  
Mohammed A. Hassan ◽  
Halima Siddiqui ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Immune Response ◽  
Adjuvant Therapy ◽  
Tumor Cells ◽  
Immune Cells ◽  
Human Leukocyte ◽  
Genetic Alterations ◽  
Programmed Death ◽  
Programmed Death 1 ◽  
Cancer Types

Among all cancer types, colorectal cancer is the third most common in men and the second most common in women globally. Generally, the risk of colorectal cancer increases with age, and colorectal cancer is modulated by various genetic alterations. Alterations in the immune response serve a significant role in the development of colorectal cancer. In primary cancer types, immune cells express a variety of inhibitory molecules that dampen the immune response against tumor cells. Additionally, few reports have demonstrated that classical chemotherapy promotes the immunosuppressive microenvironment in both tissues and immune cells. This study assessed the expression levels of genes using RT-qPCR associated with the immune system, including interferon-γ, programmed death-1, β2-microglobulin, human leukocyte antigen-A, CD3e, CD28 and intracellular adhesion molecule 1, in patients with colorectal cancer, as these genes are known to serve important roles in immune regulation during cancer incidence. Gene expression analysis was performed with the whole blood cells of patients with colorectal cancer and healthy volunteers. Compared with the normal controls, programmed death-1was highly expressed in patients with advanced-stage colorectal cancer. Furthermore, the expression of programmed death-1 was higher in patients receiving adjuvant therapy, which suggests the therapy dampened the immune response against tumor cells. The results of the present study indicate that classical adjuvant therapies, which are currently used for patients with colorectal cancer, should be modulated, and a combination of classical therapy with anti-programmed death-1 antibody should be conducted for improved management of patients with colorectal cancer.

scholarly journals Depletion of the programmed death-1 receptor completely reverses established clonal anergy in CD4+ T lymphocytes via an interleukin-2-dependent mechanism

2009 ◽  
Vol 256 (1-2) ◽  
pp. 86-91 ◽  
Author(s):  
Kenneth D. Bishop ◽  
John E. Harris ◽  
John P. Mordes ◽  
Dale L. Greiner ◽  
Aldo A. Rossini ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Interleukin 2 ◽  
Programmed Death ◽  
Programmed Death 1 ◽  
Dependent Mechanism ◽  
Clonal Anergy

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

2019 ◽  
Author(s):  
Inju Cho ◽  
Hansang Lee ◽  
Sang Eun Yoon ◽  
Kyung Ju Ryu ◽  
Young Hyeh Ko ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Tumor Cells ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Serum Levels ◽  
Large B Cell Lymphoma ◽  
Programmed Death ◽  
Programmed Death 1 ◽  
Large B Cell

Abstract Background The interaction of programmed death-1 (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.

scholarly journals Expression and clinical significance of LAG-3, FGL1, PD-L1 and CD8+T cells in hepatocellular carcinoma using Multiplex Quantitative Analysis

2020 ◽  
Author(s):  
Mengzhou Guo ◽  
Feifei Yuan ◽  
Feng Qi ◽  
Jialei Sun ◽  
Qianwen Rao ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
T Cells ◽  
Tumor Cells ◽  
Cd8 T Cells ◽  
Prognostic Significance ◽  
Normal Liver ◽  
Patient Stratification ◽  
Programmed Death ◽  
Programmed Death 1 ◽  
Low Levels

Abstract Background: fibrinogen-like protein 1 (FGL1) - Lymphocyte activating gene 3 (LAG-3) pathway is a promising immunotherapeutic target and has synergistic effect with programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1). However, the prognostic significance of FGL1-LAG-3 pathway and the correlation with PD-L1 in hepatocellular carcinoma (HCC) remain unknown.Methods: The levels of LAG-3, FGL1, PD-L1 and cytotoxic T (CD8+T) cells in 143 HCC patients were assessed by multiplex immunofluorescence. Associations between the marker’s expression and clinical significances were studied.Results: We found FGL1 and LAG-3 densities were elevated while PD-L1 and CD8 were decreased in HCC tissues compared to adjacent normal liver tissues. High levels of FGL1 were strongly associated with high densities of LAG-3+cells but not PD-L1. CD8+ T cells densities had positive correlation with PD-L1 levels and negative association with FGL1 expression. Elevated densities of LAG-3+cells and low levels of CD8+ T cells were correlated with poor disease outcome. Moreover, LAG-3+cells deteriorated patient stratification based on the abundance of CD8+ T cells. Patients with positive PD-L1 expression on tumor cells (PD-L1 TC+) tended to have an improved survival than that with negative PD-L1 expression on tumor cells (PD-L1 TC-). Furthermore, PD-L1 TC- in combination with high densities of LAG-3+cells showed the worst prognosis, and PD-L1 TC+ patients with low densities of LAG-3+cells had the best prognosis.Conclusions: LAG-3, FGL1, PD-L1 and CD8 have distinct tissue distribution and relationships with each other. High levels of LAG-3+cells and CD8+ T cells represent unfavorable and favorable prognostic biomarkers for HCC respectively.

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

2020 ◽  
Author(s):  
Inju Cho ◽  
Hansang Lee ◽  
Sang Eun Yoon ◽  
Kyung Ju Ryu ◽  
Young Hyeh Ko ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Tumor Cells ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Serum Levels ◽  
Large B Cell Lymphoma ◽  
Programmed Death ◽  
Programmed Death 1 ◽  
Large B Cell

Abstract 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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