Journal of Pathology and Translational Medicine

Original Articles

Immunohistochemical expression of programmed death-ligand 1 and CD8 in glioblastomas: Dina Mohamed El Samman, Manal Mohamed El Mahdy, Hala Sobhy Cousha, Zeinab Abd El Rahman Kamar, Khaled Abdel Karim Mohamed, Hoda Hassan Abou Gabal; J Pathol Transl Med. 2021;55(6):388-397. Published online October 14, 2021; DOI: https://doi.org/10.4132/jptm.2021.08.04

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Background
Glioblastoma is the most aggressive primary malignant brain tumor in adults and is characterized by poor prognosis. Immune evasion occurs via programmed death-ligand 1 (PD-L1)/programmed death receptor 1 (PD-1) interaction. Some malignant tumors have responded to PD-L1/PD-1 blockade treatment strategies, and PD-L1 has been described as a potential predictive biomarker. This study discussed the expression of PD-L1 and CD8 in glioblastomas.
Methods
Thirty cases of glioblastoma were stained immunohistochemically for PD-L1 and CD8, where PD-L1 expression in glioblastoma tumor tissue above 1% is considered positive and CD-8 is expressed in tumor infiltrating lymphocytes. The expression of each marker was correlated with clinicopathologic parameters. Survival analysis was conducted to correlate progression-free survival (PFS) and overall survival (OS) with PD-L1 and CD8 expression.
Results
Diffuse/fibrillary PD-L1 was expressed in all cases (mean expression, 57.6%), whereas membranous PD-L1 was expressed in six of 30 cases. CD8-positive tumor-infiltrating lymphocytes (CD8⁺ TILs) had a median expression of 10%. PD-L1 and CD8 were positively correlated (p = .001). High PD-L1 expression was associated with worse PFS and OS (p = .026 and p = .001, respectively). Correlation of CD8⁺ TILs percentage with age, sex, tumor site, laterality, and outcomes were statistically insignificant. Multivariate analysis revealed that PD-L1 was the only independent factor that affected prognosis.
Conclusions
PD-L1 expression in patients with glioblastoma is robust; higher PD-L1 expression is associated with lower CD8+ TIL expression and worse prognosis.

Citations

Citations to this article as recorded by

Tumor-associated microenvironment, PD-L1 expression and their relationship with immunotherapy in glioblastoma, IDH-wild type: A comprehensive review with emphasis on the implications for neuropathologists
Giuseppe Broggi, Giuseppe Angelico, Jessica Farina, Giordana Tinnirello, Valeria Barresi, Magda Zanelli, Andrea Palicelli, Francesco Certo, Giuseppe Barbagallo, Gaetano Magro, Rosario Caltabiano
Pathology - Research and Practice.2024; 254: 155144. CrossRef
Analysis of PD-L1 and CD3 Expression in Glioblastoma Patients and Correlation with Outcome: A Single Center Report
Navid Sobhani, Victoria Bouchè, Giovanni Aldegheri, Andrea Rocca, Alberto D’Angelo, Fabiola Giudici, Cristina Bottin, Carmine Antonio Donofrio, Maurizio Pinamonti, Benvenuto Ferrari, Stefano Panni, Marika Cominetti, Jahard Aliaga, Marco Ungari, Antonio Fi
Biomedicines.2023; 11(2): 311. CrossRef
Immuno-PET Imaging of Tumour PD-L1 Expression in Glioblastoma
Gitanjali Sharma, Marta C. Braga, Chiara Da Pieve, Wojciech Szopa, Tatjana Starzetz, Karl H. Plate, Wojciech Kaspera, Gabriela Kramer-Marek
Cancers.2023; 15(12): 3131. CrossRef

GLUT1 as a Prognostic Factor for Classical Hodgkin’s Lymphoma: Correlation with PD-L1 and PD-L2 Expression: Young Wha Koh, Jae-Ho Han, Seong Yong Park, Dok Hyun Yoon, Cheolwon Suh, Jooryung Huh; J Pathol Transl Med. 2017;51(2):152-158. Published online February 21, 2017; DOI: https://doi.org/10.4132/jptm.2016.11.03

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232 Download
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Abstract PDF

Background
Glucose transporter type 1 (GLUT1) expression is linked to glucose metabolism and tissue hypoxia. A recent study reported that GLUT1 was significantly associated with programmed death ligand 1 (PD-L1) as a therapeutic target in relapsed or refractory classical Hodgkin’s lymphoma (cHL). The purpose of this study was to measure the expression of GLUT1 and assess its prognostic significance and potential relationships with PD-L1, programmed death ligand 2 (PD-L2), and programmed death-1 (PD-1) expressions in cHL. Methods: Diagnostic tissues from 125 patients with cHL treated with doxorubicin, bleomycin, vinblastine, and dacarbazine were evaluated retrospectively via immunohistochemical analysis of GLUT1, PD-L1, PD-L2, and PD-1 expression. Results: The median follow-up time was 4.83 years (range, 0.08 to 17.33 years). GLUT1, PD-L1, PD-L2, and PD-1 were expressed in 44.8%, 63.2%, 9.6%, and 13.6% of the specimens, respectively. Positive correlations were found between GLUT1 and PD-L1 expression (p = .004) and between GLUT1 and PD-L2 expression (p = .031). GLUT1 expression in Hodgkin/Reed-Sternberg (HRS) cells was not associated with overall survival or event-free survival (EFS) in the entire cohort (p = .299 and p = .143, respectively). A subgroup analysis according to the Ann Arbor stage illustrated that GLUT1 expression in HRS cells was associated with better EFS in advanced-stage disease (p = .029). A multivariate analysis identified GLUT1 as a marginally significant prognostic factor for EFS (p = .068). Conclusions: This study suggests that GLUT1 expression is associated with better clinical outcomes in advanced-stage cHL and is significantly associated with PD-L1 and PD-L2 expressions.

Citations

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Metabolic Reprogramming and Potential Therapeutic Targets in Lymphoma
Yuyang Pang, Tingxun Lu, Zijun Y. Xu-Monette, Ken H. Young
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Peptide-based PROTAC degrader of FOXM1 suppresses cancer and decreases GLUT1 and PD-L1 expression
Kun Wang, Xiaoyong Dai, Albert Yu, Chunyan Feng, Kewei Liu, Laiqiang Huang
Journal of Experimental & Clinical Cancer Research.2022;[Epub] CrossRef
TIMP-1 Dependent Modulation of Metabolic Profiles Impacts Chemoresistance in NSCLC
Wei Xiao, Pankaj Ahluwalia, Lan Wang, John Howard, Ravindra Kolhe, Amyn M. Rojiani, Mumtaz V. Rojiani
Cells.2022; 11(19): 3036. CrossRef
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Non-invasive measurement of PD-L1 status and prediction of immunotherapy response using deep learning of PET/CT images
Wei Mu, Lei Jiang, Yu Shi, Ilke Tunali, Jhanelle E Gray, Evangelia Katsoulakis, Jie Tian, Robert J Gillies, Matthew B Schabath
Journal for ImmunoTherapy of Cancer.2021; 9(6): e002118. CrossRef
Tumor immunity is related to 18F‐FDG uptake in thymic epithelial tumor
Hisao Imai, Kyoichi Kaira, Kosuke Hashimoto, Hiroyuki Nitanda, Ryo Taguchi, Akitoshi Yanagihara, Tetsuya Umesaki, Ou Yamaguchi, Atsuto Mouri, Tomonori Kawasaki, Masanori Yasuda, Kunihiko Kobayashi, Hirozo Sakaguchi, Ichiei Kuji, Hiroshi Kagamu
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High Serum Level of Soluble Programmed Death Ligand 1 is Associated With a Poor Prognosis in Hodgkin Lymphoma
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Clinical and Translational Imaging.2018; 6(6): 417. CrossRef
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J. Han van Krieken
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PD-L1 Expression and Combined Status of PD-L1/PD-1–Positive Tumor Infiltrating Mononuclear Cell Density Predict Prognosis in Glioblastoma Patients: Jiheun Han, Yongkil Hong, Youn Soo Lee; J Pathol Transl Med. 2017;51(1):40-48. Published online December 15, 2016; DOI: https://doi.org/10.4132/jptm.2016.08.31

13,501 View
266 Download
29 Web of Science
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Abstract PDF

Background
Programmed death ligand 1 (PD-L1) in tumor cells is known to promote immune escape of cancer by interacting with programmed cell death 1 (PD-1) in tumor infiltrating immune cells. Immunotherapy targeting these molecules is emerging as a new strategy for the treatment of glioblastoma (GBM). Understanding the relationship between the PD-L1/PD-1 axis and prognosis in GBM patients may be helpful to predict the effects of immunotherapy.
Methods
PD-L1 expression and PD-1–positive tumor infiltrating mononuclear cell (PD-1+tumor infiltrating mononuclear cell [TIMC]) density were evaluated using tissue microarray containing 54 GBM cases by immunohistochemical analysis; the associations with patient clinical outcomes were evaluated.
Results
PD-L1 expression and high PD-1+TIMC density were observed in 31.5% and 50% of GBM cases, respectively. High expression of PD-L1 in tumor cells was an independent and significant predictive factor for worse overall survival (OS; hazard ratio, 4.958; p = .007) but was not a significant factor in disease-free survival (DFS). PD-1+TIMC density was not correlated with OS or DFS. When patients were classified based on PD-1 expression and PD-1+TIMC density, patients with PD-L1+/PD-1+TIMC low status had the shortest OS (13 months, p = .009) and DFS (7 months, p = .053).
Conclusions
PD-L1 expression in GBM was an independent prognostic factor for poor OS. In addition, combined status of PD-L1 expression and PD-1+TIMC density also predicted patient outcomes, suggesting that the therapeutic role of the PD-1/PD-L1 axis should be considered in the context of GBM immunity.

Citations

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Tumor-associated microenvironment, PD-L1 expression and their relationship with immunotherapy in glioblastoma, IDH-wild type: A comprehensive review with emphasis on the implications for neuropathologists
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