Immune Profiling and Quantitative Analysis Decipher the Clinical Role of Immune-Checkpoint Expression in the Tumor Immune Microenvironment of DLBCL
| العنوان: | Immune Profiling and Quantitative Analysis Decipher the Clinical Role of Immune-Checkpoint Expression in the Tumor Immune Microenvironment of DLBCL |
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| المؤلفون: | Hongwei Zhang, Karen Dybkær, Miguel A. Piris, Alexandar Tzankov, Jason R. Westin, Ziju Y. Xu-Monette, Jing Wang, Carlo Visco, Jane N. Winter, Maurilio Ponzoni, L. Jeffrey Medeiros, Yi Miao, Ganiraju C. Manyam, Bing Xu, Yong Li, Min Xiao, Hua You, Nicholas Hoe, Gordon J. Freeman, Raúl Torres-Ruiz, Andrés J.M. Ferreri, Wayne Tam, Ken H. Young, Qingyan Au, Govind Bhagat, George Z. Rassidakis, Xiaohong Tan, Eric D. Hsi, Sandra Rodriguez-Perales, Raghav Padmanabhan, Lan V. Pham, Michael Boe Møller, J. Han van Krieken |
| المساهمون: | Xu-Monette, Z. Y., Xiao, M., Au, Q., Padmanabhan, R., Xu, B., Hoe, N., Rodriguez-Perales, S., Torres-Ruiz, R., Manyam, G. C., Visco, C., Miao, Y., Tan, X., Zhang, H., Tzankov, A., Wang, J., Dybkaer, K., Tam, W., You, H., Bhagat, G., Hsi, E. D., Ponzoni, M., Ferreri, A. J. M., Moller, M. B., Piris, M. A., Han van Krieken, J., Winter, J. N., Westin, J. R., Pham, L. V., Jeffrey Medeiros, L., Rassidakis, G. Z., Li, Y., Freeman, G. J., Young, K. H. |
| المصدر: | Xu-Monette, Z Y, Xiao, M, Au, Q, Padmanabhan, R, Xu, B, Hoe, N, Rodríguez-Perales, S, Torres-Ruiz, R, Manyam, G C, Visco, C, Miao, Y, Tan, X, Zhang, H, Tzankov, A, Wang, J, Dybkær, K, Tam, W, You, H, Bhagat, G, Hsi, E D, Ponzoni, M, Ferreri, A J M, Møller, M B, Piris, M A, van Krieken, J H, Winter, J N, Westin, J R, Pham, L V, Medeiros, L J, Rassidakis, G Z, Li, Y, Freeman, G J & Young, K H 2019, ' Immune Profiling and Quantitative Analysis Decipher the Clinical Role of Immune-Checkpoint Expression in the Tumor Immune Microenvironment of DLBCL ', Cancer Immunology Research, vol. 7, no. 4, pp. 644-657 . https://doi.org/10.1158/2326-6066.CIR-18-0439Test Cancer Immunology Research, 7, 644-657 Cancer Immunology Research, 7, 4, pp. 644-657 Xu-Monette, Z, Xiao, M, Au, Q, Padmanabhan, R, Xu, B, Hoe, N, Rodriguez-Perales, S, Torres-Ruiz, R, Manyam, G, Visco, C, Miao, Y, Tan, X, Zhang, H, Tzankov, A, Wang, J, Dybkaer, K, Tam, W, You, H, Bhagat, G, Hsi, E D, Ponzoni, M, Ferreri, A J M, Møller, M B, Piris, M A, van Krieken, J H, Winter, J N, Westin, J R, Pham, L V, Medeiros, L J, Rassidakis, G Z, Li, Y, Freeman, G J & Young, K H 2019, ' Immune profiling and quantitative analysis decipher the clinical role of immune checkpoint expression in the tumor immune microenvironment of DLBCL ', Cancer Immunology Research, vol. 7, no. 4, pp. 644-657 . https://doi.org/10.1158/2326-6066.CIR-18-0439Test |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, Cancer Research, Vincristine, Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2], T-Lymphocytes, Programmed Cell Death 1 Receptor, Immunology, B7-H1 Antigen, CHI3L1, 03 medical and health sciences, All institutes and research themes of the Radboud University Medical Center, Antineoplastic Agents, Immunological, 0302 clinical medicine, Immune system, immune system diseases, hemic and lymphatic diseases, Antineoplastic Combined Chemotherapy Protocols, Tumor Microenvironment, medicine, Humans, Neoplasm, CTLA-4 Antigen, Cyclophosphamide, CD20, biology, business.industry, Middle Aged, Prognosis, medicine.disease, Immune checkpoint, Lymphoma, Gene Expression Regulation, Neoplastic, Killer Cells, Natural, PD1, Phenotype, 030104 developmental biology, Doxorubicin, Drug Resistance, Neoplasm, 030220 oncology & carcinogenesis, Cancer research, biology.protein, Prednisone, Lymphoma, Large B-Cell, Diffuse, Rituximab, business, CD8, medicine.drug |
| الوصف: | PD-1/L1 and CTLA-4 blockade immunotherapies have been approved for 13 types of cancers and are being studied in diffuse large B-cell lymphoma (DLBCL), the most common aggressive B-cell lymphoma. However, whether both PD-1 and CTLA-4 checkpoints are active and clinically significant in DLBCL is unknown. Whether PD-1 ligands expressed by tumor cells or by the microenvironment of DLBCL are critical for the PD-1 immune checkpoint is unclear. We performed immunophenotypic profiling for 405 patients with de novo DLBCL using a MultiOmyx immunofluorescence platform and simultaneously quantitated expression/coexpression of 13 immune markers to identify prognostic determinants. In both training and validation cohorts, results demonstrated a central role of the tumor immune microenvironment, and when its functionality was impaired by deficiency in tumor-infiltrating T cells and/or natural killer cells, high PD-1 expression (but not CTLA-4) on CD8+ T cells, or PD-L1 expression on T cells and macrophages, patients had significantly poorer survival after rituximab–CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) immunochemotherapy. In contrast, tumor-cell PD-L2 expression was associated with superior survival, as well as PD-L1+CD20+ cells proximal (indicates interaction) to PD-1+CD8+ T cells in patients with low PD-1+ percentage of CD8+ T cells. Gene-expression profiling results suggested the reversibility of T-cell exhaustion in PD-1+/PD-L1+ patients with unfavorable prognosis and implication of LILRA/B, IDO1, CHI3L1, and SOD2 upregulation in the microenvironment dysfunction with PD-L1 expression. This study comprehensively characterized the DLBCL immune landscape, deciphered the differential roles of various checkpoint components in rituximab–CHOP resistance in DLBCL patients, and suggests targets for PD-1/PD-L1 blockade and combination immunotherapies. |
| اللغة: | English |
| تدمد: | 2326-6066 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::dd2bda5c650a913672e02e5151bffdabTest http://hdl.handle.net/11562/1011409Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....dd2bda5c650a913672e02e5151bffdab |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 23266066 |
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