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.

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.

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.

scholarly journals Expression of Immune Checkpoint Regulators IDO, VISTA, LAG3, and TIM3 in Resected Pancreatic Ductal Adenocarcinoma

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2689
Author(s):  
Felix Popp ◽  
Ingracia Capino ◽  
Joana Bartels ◽  
Alexander Damanakis ◽  
Jiahui Li ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Immune Checkpoint ◽  
Patient Survival ◽  
Checkpoint Inhibitors ◽  
Tumor Infiltrating Lymphocytes ◽  
Ductal Adenocarcinoma ◽  
Lymph Node Status ◽  
Clinicopathologic Parameters ◽  
Survival Differences ◽  
Infiltrating Lymphocytes

Pancreatic cancer features elaborate mechanisms of immune evasion. The potential of new immune molecules was explored to restore the antitumor immune response. If these immune molecules are associated with poor survival, specific drugs could take effect. Here, we analyze the expression of VISTA, LAG3, IDO, and TIM3 on tumor-infiltrating lymphocytes (TILs) and its impact on patient survival. We analyzed 153 pancreatic cancer patients from the prospectively managed database of the multicentered PANCALYZE study. Immunohistochemistry on a tissue microarray assessed VISTA, LAG3, IDO, and TIM3 expression of TILs from the patients undergoing primary resection. Complementarily, we analyzed publicly available transcriptomic data (n = 903). Successful completion of chemotherapy, and lymph node status were independent predictors of survival in the multivariate analysis of the clinicopathologic parameters. Fifteen tumors were exclusively VISTA-positive, thirteen tumors expressed VISTA together with TIM3, and ten tumors expressed VISTA together with IDO. Patients featuring tumors with high numbers of IDO-positive TILs had better patient survival (p = 0.037). VISTA, LAG3, and TIM3 expression did not correlate with survival. The analysis of publicly available data did not show survival differences. Tumors rarely co-express more than two immune molecules at the same time, and VISTA is most frequently co-expressed. Although IDO generally inhibits T-cell proliferation, a high expression of IDO was associated with improved survival. We expect immune checkpoint inhibitors against VISTA, LAG3, and TIM3 to be inefficient in a clinical application.

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