scholarly journals PD-L1 Expression and Tumor-Infiltrating Lymphocytes in Thymic Epithelial Neoplasms

2019 ◽  
Vol 8 (11) ◽  
pp. 1833 ◽  
Author(s):  
Higuchi ◽  
Goto ◽  
Hirotsu ◽  
Nakagomi ◽  
Yokoyama ◽  
...  
Keyword(s):  
Malignant Tumors ◽  
Tumor Infiltrating Lymphocytes ◽  
Clinicopathological Parameters ◽  
Mediastinal Tumors ◽  
Thymic Epithelial Tumors ◽  
Programmed Death ◽  
Programmed Death 1 ◽  
Promising Treatment ◽  
Type Ab ◽  
Infiltrating Lymphocytes

Thymic epithelial tumors (TETs) are rare malignant mediastinal tumors that are difficult to diagnose and treat. The programmed death 1 (PD-1) receptor and its ligand (PD-L1) are expressed in various malignant tumors and have emerged as potential immunotherapeutic targets. However, the immunobiology of TETs is poorly understood. We evaluated PD-L1 expression and the presence of tumor-infiltrating lymphocytes (CD8 and CD3 expression) in surgical TET specimens from 39 patients via immunohistochemistry and determined their relation to clinicopathological parameters. Cases with membranous reactivity of the PD-L1 antibody in ≥1% of tumor cells were considered positive. Positive PD-L1 expression was observed in 53.9% of cases. Histologically, PD-L1 expression was positive in 2/6 type A, 2/6 type AB, 3/9 type B1, 4/4 type B2, 5/6 type B3, and 5/8 type C TET cases. Thus, the number of cases with PD-L1 expression and the percent expression of PD-L1 were significantly higher in more aggressive thymomas (type B2 or B3). CD3+ and CD8+ tumor-infiltrating lymphocytes were diffusely and abundantly distributed in all cases. These data suggest that a PD-1/PD-L1 blockade is a promising treatment for TETs, with more beneficial treatment effects for aggressive thymomas such as type B2 or B3.

scholarly journals Immune checkpoint markers in gastroenteropancreatic neuroendocrine neoplasia

2019 ◽  
Vol 26 (3) ◽  
pp. 293-301 ◽  
Author(s):  
Florian Bösch ◽  
Katharina Brüwer ◽  
Annelore Altendorf-Hofmann ◽  
Christoph J Auernhammer ◽  
Christine Spitzweg ◽  
...  
Keyword(s):  
Patient Survival ◽  
Tumor Infiltrating Lymphocytes ◽  
Cell Surface Receptor ◽  
Clinicopathological Parameters ◽  
Term Survival ◽  
Programmed Death ◽  
Promising Therapeutic Approach ◽  
Surface Receptor ◽  
Programmed Death 1 ◽  
Infiltrating Lymphocytes

Cancer immunotherapy has evolved major breakthroughs in the last years. The cell-surface receptor programmed death-1 (PD-1) and its ligand, programmed death ligand-1 (PD-L1), have been detected in various cancer types. However, the analysis on gastroenteropancreatic neoplasia (GEP-NENs) is limited. Therefore, the aim of this study was to characterize GEP-NENs with regard to PD-1/PD-L1 pathway and tumor-infiltrating lymphocytes (TILs). On protein level, we examined TILs, PD-1 and PD-L1 expression in tumor tissue of 244 GEP-NENs using immunohistochemistry. Expression levels were correlated with clinicopathological parameters including long-term survival in an observational study. In total, 244 patients could be included. Most of the patients had a NEN of the small intestine (52.5%) or the pancreas (29.5%). All tumors could be graded by their morphology and Ki67 index, with 57.8% G1, 34% G2 and 8.2% G3 tumors. High TILs (19.6%) and high PD-1 (16.1%) expression showed a significant correlation with shorter patient survival (P < 0.05) and with a higher grading. Furthermore, expression of PD-L1 (8.7%) showed a trend to shorter patient survival. High TILs and PD-1 expression are significantly associated with shorter patient survival and higher grading in GEP-NENs. PD-L1 expression showed a trend to shorter patient survival. Immunotherapy might be a promising therapeutic approach in GEP-NENs especially in tumors with high TILs.

PD-1/PDL-1 Inhibitors as Immunotherapy for Ovarian Cancer

2018 ◽  
Author(s):  
Scott Moerdler ◽  
Xingxing Zang
Keyword(s):  
Ovarian Cancer ◽  
T Cell Activation ◽  
Cell Activation ◽  
Immune Escape ◽  
Tumor Infiltrating Lymphocytes ◽  
Immunoglobulin Superfamily ◽  
Combination Therapies ◽  
Programmed Death ◽  
Programmed Death 1 ◽  
Infiltrating Lymphocytes

Programmed death 1 (PD-1), a member of the B7-CD28 immunoglobulin superfamily, and its ligands PD-L1/PD-L2 inhibit T-cell activation. They also play a key role in the tumor microenvironment, allowing for cancer immune escape. PD-1 is induced on a variety of immune cells, including tumor-infiltrating lymphocytes (TILs), while PD-L1 is found on many types of solid tumors including ovarian cancer and some TILs. The use of immunocheckpoint inhibitors like anti-PD-1 and anti-PD-L1 therapies has been shown to reactivate the immune system to attack tumor cells. Ovarian cancers have been shown to be responsive to anti-PD-1 and anti-PD-L1 therapies, though immunocheckpoint inhibitors are not enough. Current research is evaluating combination therapies to improve response rates.

scholarly journals Positive PD-L1 Expression Predicts Worse Outcome in Cutaneous Angiosarcoma

2017 ◽  
Vol 3 (4) ◽  
pp. 360-369 ◽  
Author(s):  
Akira Shimizu ◽  
Kyoichi Kaira ◽  
Yuko Okubo ◽  
Daisuke Utsumi ◽  
Masahito Yasuda ◽  
...  
Keyword(s):  
Clinical Stage ◽  
Tumor Infiltrating Lymphocytes ◽  
Tumor Proliferation ◽  
Ki 67 ◽  
Positive Expression ◽  
Programmed Death ◽  
Clinicopathological Significance ◽  
Programmed Death 1 ◽  
Infiltrating Lymphocytes ◽  
Clinicopathological Variables

Purpose Programmed death-1 (PD-1) or programmed death ligand-1 (PD-L1) targeted therapies have shown promising survival outcomes in several human neoplasms. However, it is unclear whether the expression of PD-L1 can be correlated to any clinical and pathologic variables in patients with cutaneous angiosarcoma (CA). The aim of this study was to evaluate the clinicopathological significance of PD-L1 expression in CA patients. Materials and Methods Data from 52 patients with CA were retrospectively reviewed. PD-L1 expression, tumor proliferation determined by Ki-67 index, and immunohistochemical evaluation of tumor-infiltrating lymphocytes, CD4+ and CD8+, were used to determine correlation with clinicopathological variables. Results PD-L1 was positively expressed in 40% of all patients. PD-L1 expression was significantly associated with tumor cell proliferation. Multivariate analysis confirmed that high levels of CD8+ tumor-infiltrating lymphocytes were a significant predictor in patients with clinical stage I CA and the positive expression of PD-L1 was an independent prognostic factor in predicting worse outcome. Conclusion PD-L1 expression is a novel pathologic marker for predicting worse outcome in patients with CA.

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