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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
  • 2,178 View
  • 118 Download
  • 1 Citations
AbstractAbstract PDF
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.
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.
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.
PD-L1 expression in patients with glioblastoma is robust; higher PD-L1 expression is associated with lower CD8+ TIL expression and worse prognosis.


Citations to this article as recorded by  
  • 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
The Major Role of NF-κB in the Depth of Invasion on Acral Melanoma by Decreasing CD8+ T Cells
Hermin Aminah Usman, Bethy S. Hernowo, Maringan Diapari Lumban Tobing, Reti Hindritiani
J Pathol Transl Med. 2018;52(3):164-170.   Published online April 20, 2018
  • 4,969 View
  • 107 Download
  • 6 Citations
AbstractAbstract PDF
The tumor microenvironment including immune surveillance affects malignant melanoma (MM) behavior. Nuclear factor κB (NF-κB) stimulates the transcription of various genes in the nucleus and plays a role in the inflammatory process and in tumorigenesis. CD8+ T cells have cytotoxic properties important in the elimination of tumors. However, inhibitory receptors on the cell surface will bind to programmed death-ligand 1 (PD-L1), causing CD8+ T cells to lose their ability to initiate an immune response. This study analyzed the association of NF-κB and PD-L1 expression levels and CD8+ T-cell counts with depth of invasion of acral MM, which may be a predictor of aggressiveness related to an increased risk of metastasis.
A retrospective cross-sectional study was conducted in the Department of Anatomical Pathology, Faculty of Medicine, Universitas Padjadjaran/Hasan Sadikin Hospital using 96 cases of acral melanoma. Immunohistochemical staining was performed on paraffin blocks using anti–NF-κB, –PD-L1, and -CD8 antibodies and invasion depth was measured using dotSlide-imaging software.
The study showed significant associations between the individual expression of NF-κB and PD-L1 and CD8+ T-cell number, with MM invasion depth. NF-κB was found to be a confounding variable of CD8+ T-cell number (p < .05), but not for PD-L1 expression (p = .154). Through multivariate analysis it was found that NF-κB had the greatest association with the depth of invasion (p < .001), whereas PD-L1 was unrelated to the depth of invasion because it depends on the number of CD8+ T cells (p = .870).
NF-κB plays a major role in acral MM invasion, by decreasing the number of CD8+ T cells in acral MM.


Citations to this article as recorded by  
  • Possible Mechanisms of Oxidative Stress-Induced Skin Cellular Senescence, Inflammation, and Cancer and the Therapeutic Potential of Plant Polyphenols
    Hui-Min Liu, Ming-Yan Cheng, Meng-Han Xun, Zhi-Wei Zhao, Yun Zhang, Wei Tang, Jun Cheng, Jia Ni, Wei Wang
    International Journal of Molecular Sciences.2023; 24(4): 3755.     CrossRef
  • Clinical features, molecular pathology, and immune microenvironmental characteristics of acral melanoma
    Jianping Gui, Zhen Guo, Di Wu
    Journal of Translational Medicine.2022;[Epub]     CrossRef
  • High Expression of COX-2 Associated with the Depth of Invasion on Acral Melanoma by Increasing TGF-β1
    Nastassa Gipsyianti, Afiati Aziz, Bethy S Hernowo, Hermin A Usman
    Clinical, Cosmetic and Investigational Dermatology.2021; Volume 14: 209.     CrossRef
  • More than just acral melanoma: the controversies of defining the disease
    Sara S Bernardes, Ingrid Ferreira, David E Elder, Aretha B Nobre, Héctor Martínez‐Said, David J Adams, Carla Daniela Robles‐Espinoza, Patricia A Possik
    The Journal of Pathology: Clinical Research.2021; 7(6): 531.     CrossRef
  • CD103+ T Lymphocyte Count Linked to the Thickness of Invasion on Acral Melanoma without E-Cadherin Involvement
    Fauzan Ali Zainal Abidin, Hermin Aminah Usman, Sri Suryanti, Bethy S Hernowo
    Clinical, Cosmetic and Investigational Dermatology.2021; Volume 14: 1783.     CrossRef
  • Translational pathology, genomics and the development of systemic therapies for acral melanoma
    Yian Ann Chen, Jamie K. Teer, Zeynep Eroglu, Jheng-Yu Wu, John M. Koomen, Florian A. Karreth, Jane L. Messina, Keiran S.M. Smalley
    Seminars in Cancer Biology.2020; 61: 149.     CrossRef
Progressive Increase of Regulatory T Cells and Decrease of CD8+ T Cells and CD8+ T Cells/Regulatory T Cells Ratio during Colorectal Cancer Development
Tae Jung Jang
Korean J Pathol. 2013;47(5):443-451.   Published online October 25, 2013
  • 7,322 View
  • 49 Download
  • 23 Citations
AbstractAbstract PDF

We examined the distribution of CD8+ T cells and regulatory T cells (Tregs), measured the CD8+ T cell/Tregs ratio, investigated the relationship between Tregs and cyclooxygenase-2 (COX-2) expression during colorectal cancer (CRC) development.


We performed immunohistochemical staining for CD8, forkhead box P3, E-cadherin, and COX-2 in 32 cases of invasive CRC, 10 cases of intramucosal CRC, 27 cases of high-grade tubular adenoma, 22 cases of low-grade tubular adenoma, and 32 cases of non-neoplastic conditions.


We observed a progressive increase in Tregs, and a decrease in CD8+ T cells and the CD8+ T cells/Tregs ratio during CRC development. The alterations were most severe in high-grade tubular adenoma and CRC. COX-2 expression was positively associated with Tregs infiltration. The degree of T cell infiltration differed among tumor compartment and the ratio in the tumor center was the lowest of all areas. The ratio and number of CD8+ T cells in the tumor center and the invasive front of invasive CRC were associated with gender, differentiation, node metastasis and tumor budding.


Alteration in the distribution of both CD8+T cells and Tregs may contribute to the generation of an immune environment suitable for the development and progression of CRC.


Citations to this article as recorded by  
  • Tumor Microenvironment and Immune Response in Lip Cancer
    Anastasia G. Gkegka, Michael I. Koukourakis, Maria Lambropoulou, Alexandra Giatromanolaki
    Cancers.2023; 15(5): 1478.     CrossRef
  • Molecular mechanisms of tumour budding and its association with microenvironment in colorectal cancer
    Phimmada Hatthakarnkul, Jean A. Quinn, Aula Ammar, Gerard Lynch, Hester Van Wyk, Donald C. McMillan, Chanitra Thuwajit, Joanne Edwards
    Clinical Science.2022; 136(8): 521.     CrossRef
  • Attackers and defenders: tumor buds and lymphocytes as morphological biomarkers in colorectal cancer
    Sonay Kus Öztürk, Tariq S. Haddad, Inti Zlobec, Alessandro Lugli, Iris D. Nagtegaal
    Diagnostic Histopathology.2022; 28(11): 480.     CrossRef
  • The prognostic impact of the immune microenvironment in small-cell neuroendocrine carcinoma of the uterine cervix: PD-L1 and immune cell subtypes
    Xiaoying Sun, Lili Liu, Ting Wan, Qidan Huang, Jieping Chen, Rongzhen Luo, Jihong Liu
    Cancer Cell International.2022;[Epub]     CrossRef
  • Preinvasive Colorectal Lesions of African Americans Display an Immunosuppressive Signature Compared to Caucasian Americans
    Kristin Wallace, Georges J. Nahhas, Christine Bookhout, David N. Lewin, Chrystal M. Paulos, Nana Nikolaishvili-Feinberg, Stephanie M. Cohen, Silvia Guglietta, Ali Bakhtiari, E. Ramsay Camp, Elizabeth G. Hill, John A. Baron, Jennifer D. Wu, Alexander V. Al
    Frontiers in Oncology.2021;[Epub]     CrossRef
  • Cancer Immunoprevention: Current Status and Future Directions
    Mahsa Keshavarz-Fathi, Nima Rezaei
    Archivum Immunologiae et Therapiae Experimentalis.2021;[Epub]     CrossRef
  • Transcriptomic Analyses of the Adenoma-Carcinoma Sequence Identify Hallmarks Associated With the Onset of Colorectal Cancer
    Qin Hong, Bing Li, Xiumei Cai, Zhengtao Lv, Shilun Cai, Yunshi Zhong, Bo Wen
    Frontiers in Oncology.2021;[Epub]     CrossRef
  • Immune Responses Vary in Preinvasive Colorectal Lesions by Tumor Location and Histology
    Kristin Wallace, Georges J. El Nahas, Christine Bookhout, Jessica E. Thaxton, David N. Lewin, Nana Nikolaishvili-Feinberg, Stephanie M. Cohen, J. Grant Brazeal, Elizabeth G. Hill, Jennifer D. Wu, John A. Baron, Alexander V. Alekseyenko
    Cancer Prevention Research.2021; 14(9): 885.     CrossRef
  • CD103+ T Lymphocyte Count Linked to the Thickness of Invasion on Acral Melanoma without E-Cadherin Involvement
    Fauzan Ali Zainal Abidin, Hermin Aminah Usman, Sri Suryanti, Bethy S Hernowo
    Clinical, Cosmetic and Investigational Dermatology.2021; Volume 14: 1783.     CrossRef
  • FOXP3 and CD25 double staining antibody cocktails identify regulatory T cells in different types of tumor tissues using tissue microarrays
    Xinmin Liu, Xiaohong Wang, Jianmin Ding, Yan Gao, Yiming Zhao, Ruihua Zhao, Qigang Sun, Songlin Zhang
    Annals of Diagnostic Pathology.2019; 38: 67.     CrossRef
  • Epithelial CD80 promotes immune surveillance of colonic preneoplastic lesions and its expression is increased by oxidative stress through STAT3 in colon cancer cells
    Chiara Marchiori, Melania Scarpa, Andromachi Kotsafti, Susan Morgan, Matteo Fassan, Vincenza Guzzardo, Andrea Porzionato, Imerio Angriman, Cesare Ruffolo, Stefania Sut, Stefano Dall’Acqua, Romeo Bardini, Raffaele De Caro, Carlo Castoro, Marco Scarpa, Igna
    Journal of Experimental & Clinical Cancer Research.2019;[Epub]     CrossRef
  • Automated Analysis of Lymphocytic Infiltration, Tumor Budding, and Their Spatial Relationship Improves Prognostic Accuracy in Colorectal Cancer
    Ines P. Nearchou, Kate Lillard, Christos G. Gavriel, Hideki Ueno, David J. Harrison, Peter D. Caie
    Cancer Immunology Research.2019; 7(4): 609.     CrossRef
  • Colorectal cancer prevention: Immune modulation taking the stage
    Rochelle Fletcher, Yi-Jun Wang, Robert E. Schoen, Olivera J. Finn, Jian Yu, Lin Zhang
    Biochimica et Biophysica Acta (BBA) - Reviews on Cancer.2018; 1869(2): 138.     CrossRef
  • The Major Role of NF-κB in the Depth of Invasion on Acral Melanoma by Decreasing CD8+ T Cells
    Hermin Aminah Usman, Bethy S. Hernowo, Maringan Diapari Lumban Tobing, Reti Hindritiani
    Journal of Pathology and Translational Medicine.2018; 52(3): 164.     CrossRef
  • Increased number of arginase 1-positive cells in the stroma of carcinomas compared to precursor lesions and nonneoplastic tissues
    Tae Jung Jang, Sun A. Kim, Min Kyung Kim
    Pathology - Research and Practice.2018; 214(8): 1179.     CrossRef
  • Hematopoietic stem cell specific V-ATPase controls breast cancer progression and metastasis via cytotoxic T cells
    Manoranjan Sahoo, Gajendra K. Katara, Mahmood Y. Bilal, Safaa A. Ibrahim, Arpita Kulshrestha, Sara Fleetwood, Kimiko Suzue, Kenneth D. Beaman
    Oncotarget.2018; 9(69): 33215.     CrossRef
  • Morphoproteomic-Guided Host-Directed Therapy for Tuberculosis
    Robert E. Brown, Robert L. Hunter, Shen-An Hwang
    Frontiers in Immunology.2017;[Epub]     CrossRef
  • O-GlcNAcylation is associated with the development and progression of gastric carcinoma
    Tae Jung Jang, Ui Jung Kim
    Pathology - Research and Practice.2016; 212(7): 622.     CrossRef
  • The Immune Landscapes of Polypoid and Nonpolypoid Precancerous Colorectal Lesions
    Antonella Maglietta, Rosalia Maglietta, Teresa Staiano, Ramona Bertoni, Nicola Ancona, Giancarlo Marra, Leonardo Resta, Hiroshi Shiku
    PLOS ONE.2016; 11(7): e0159373.     CrossRef
  • Analysis of CD8+ Treg cells in patients with ovarian cancer: a possible mechanism for immune impairment
    Shuping Zhang, Xing Ke, Suyun Zeng, Meng Wu, Jianfang Lou, Lei Wu, Peijun Huang, Lei Huang, Fang Wang, Shiyang Pan
    Cellular & Molecular Immunology.2015; 12(5): 580.     CrossRef
  • The Distribution of CD8- and Foxp3-positive T Cells in Skin Squamous Cell Tumors and Basal Cell Carcinomas
    Tae Jung Jang
    Journal of Life Science.2015; 25(6): 686.     CrossRef
  • Correlation between infiltration of FOXP3+ regulatory T cells and expression of B7-H1 in the tumor tissues of gastric cancer
    Jingying Hou, Zhong Yu, Rengyun Xiang, Chuqiang Li, Lin Wang, Shufen Chen, Qingyun Li, Mei Chen, Linyun Wang
    Experimental and Molecular Pathology.2014; 96(3): 284.     CrossRef
  • Methionine enkephalin (MENK) improves lymphocyte subpopulations in human peripheral blood of 50 cancer patients by inhibiting regulatory T cells (Tregs)
    Qiushi Wang, Xinghua Gao, Zhe Yuan, Zhe Wang, Yiming Meng, Yan Cao, Nicolas P Plotnikoff, Noreen Griffin, Fengping Shan
    Human Vaccines & Immunotherapeutics.2014; 10(7): 1836.     CrossRef

JPTM : Journal of Pathology and Translational Medicine