Molecular characteristics of immunocytes infiltration in primary central nervous system lymphoma

Background: Primary central nervous system lymphoma (PCNSL) is a rare B-cell lymphoma of central nervous system, which is often found in immunocompromised patients. The common clinical treatment of PCNSL is methotrexate (MTX) and whole brain radiation therapy. With the development of tumour immunolo...

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Main Authors: Linyun Zhang, Fei Sun, Xiaona Lu, Xiaotong Wang, Jie Wang, Jun Li, Yingsong Xu, Daqing Kou, Hongtao Lv, Bin Don
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-08-01
Series:Frontiers in Genetics
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fgene.2022.921823/full
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author Linyun Zhang
Fei Sun
Xiaona Lu
Xiaotong Wang
Jie Wang
Jun Li
Yingsong Xu
Daqing Kou
Hongtao Lv
Bin Don
author_facet Linyun Zhang
Fei Sun
Xiaona Lu
Xiaotong Wang
Jie Wang
Jun Li
Yingsong Xu
Daqing Kou
Hongtao Lv
Bin Don
author_sort Linyun Zhang
collection DOAJ
description Background: Primary central nervous system lymphoma (PCNSL) is a rare B-cell lymphoma of central nervous system, which is often found in immunocompromised patients. The common clinical treatment of PCNSL is methotrexate (MTX) and whole brain radiation therapy. With the development of tumour immunology research, the tumour microenvironment of PCNSL is characterised by abnormal expression of different immune signature molecules and patients with PCNSL may benefit from tumour immunotherapy.Methods: In our research, RNA-seq data from 82 PCNSL patients were collated by mining the microarray data from the GEO database. All samples were classified into three types related to tumour immune response by the Cibersort algorithm and consistent clustering. Differential analysis of genes was used to uncover 2 sets of differential genes associated with tumour immunity. The ICI scores of each sample were obtained by PCA algorithm, and the relationship between ICI scores and immune checkpoint expression, immunotherapy and drug sensitivity was investigated. Genes associated with ICI scores and their functional characteristics were investigated by WGCNA analysis and PPI analysis, based on the ICI scores of each sample.Results: The tumour microenvironment in PCNSL has a greater relationship with the tumour immune response. ICI scores obtained from 375 differential genes were associated with multiple immune responses in PCNSL. PCNSL patients with higher ICI scores had a better tumour microenvironment and were sensitive to immunotherapy and some small molecule drug. This study also identified 64 genes associated with ICI scores, which may serve as important therapeutic and prognostic targets for PCNSL.Conclusion: The presence of multiple immunosuppressive responses in the tumour microenvironment of PCNSL which suggested that improving the immune function of PCNSL patients through immunotherapy and targeted therapies can be an effective treatment for PCNSL. And the ICI score and associated genes may also provide a better predictor of the clinical use of immunotherapy.
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spelling doaj.art-61ea2b168fcd4659a06396faae92110a2022-12-22T03:44:32ZengFrontiers Media S.A.Frontiers in Genetics1664-80212022-08-011310.3389/fgene.2022.921823921823Molecular characteristics of immunocytes infiltration in primary central nervous system lymphomaLinyun Zhang0Fei Sun1Xiaona Lu2Xiaotong Wang3Jie Wang4Jun Li5Yingsong Xu6Daqing Kou7Hongtao Lv8Bin Don9Department of Neurosurgery, First Affiliated Hospital of Dalian Medical University, Dalian, ChinaDepartment of Neurosurgery, First Affiliated Hospital of Dalian Medical University, Dalian, ChinaInstitute of Cancer Stem Cell, Dalian Medical University, Dalian, ChinaDepartment of Neurosurgery, First Affiliated Hospital of Dalian Medical University, Dalian, ChinaDepartment of Neurosurgery, First Affiliated Hospital of Dalian Medical University, Dalian, ChinaDepartment of Neurosurgery, First Affiliated Hospital of Dalian Medical University, Dalian, ChinaDepartment of Surgery, First Affiliated Hospital of Dalian Medical University, Dalian, ChinaDepartment of Clinical Laboratory, First Affiliated Hospital of Dalian Medical University, Dalian, ChinaDepartment of Neurosurgery, First Affiliated Hospital of Dalian Medical University, Dalian, ChinaDepartment of Neurosurgery, First Affiliated Hospital of Dalian Medical University, Dalian, ChinaBackground: Primary central nervous system lymphoma (PCNSL) is a rare B-cell lymphoma of central nervous system, which is often found in immunocompromised patients. The common clinical treatment of PCNSL is methotrexate (MTX) and whole brain radiation therapy. With the development of tumour immunology research, the tumour microenvironment of PCNSL is characterised by abnormal expression of different immune signature molecules and patients with PCNSL may benefit from tumour immunotherapy.Methods: In our research, RNA-seq data from 82 PCNSL patients were collated by mining the microarray data from the GEO database. All samples were classified into three types related to tumour immune response by the Cibersort algorithm and consistent clustering. Differential analysis of genes was used to uncover 2 sets of differential genes associated with tumour immunity. The ICI scores of each sample were obtained by PCA algorithm, and the relationship between ICI scores and immune checkpoint expression, immunotherapy and drug sensitivity was investigated. Genes associated with ICI scores and their functional characteristics were investigated by WGCNA analysis and PPI analysis, based on the ICI scores of each sample.Results: The tumour microenvironment in PCNSL has a greater relationship with the tumour immune response. ICI scores obtained from 375 differential genes were associated with multiple immune responses in PCNSL. PCNSL patients with higher ICI scores had a better tumour microenvironment and were sensitive to immunotherapy and some small molecule drug. This study also identified 64 genes associated with ICI scores, which may serve as important therapeutic and prognostic targets for PCNSL.Conclusion: The presence of multiple immunosuppressive responses in the tumour microenvironment of PCNSL which suggested that improving the immune function of PCNSL patients through immunotherapy and targeted therapies can be an effective treatment for PCNSL. And the ICI score and associated genes may also provide a better predictor of the clinical use of immunotherapy.https://www.frontiersin.org/articles/10.3389/fgene.2022.921823/fullprimary central nervous system lymphomatumour immune microenvironmentnetwork analysischemotherapyimmunotherapy
spellingShingle Linyun Zhang
Fei Sun
Xiaona Lu
Xiaotong Wang
Jie Wang
Jun Li
Yingsong Xu
Daqing Kou
Hongtao Lv
Bin Don
Molecular characteristics of immunocytes infiltration in primary central nervous system lymphoma
Frontiers in Genetics
primary central nervous system lymphoma
tumour immune microenvironment
network analysis
chemotherapy
immunotherapy
title Molecular characteristics of immunocytes infiltration in primary central nervous system lymphoma
title_full Molecular characteristics of immunocytes infiltration in primary central nervous system lymphoma
title_fullStr Molecular characteristics of immunocytes infiltration in primary central nervous system lymphoma
title_full_unstemmed Molecular characteristics of immunocytes infiltration in primary central nervous system lymphoma
title_short Molecular characteristics of immunocytes infiltration in primary central nervous system lymphoma
title_sort molecular characteristics of immunocytes infiltration in primary central nervous system lymphoma
topic primary central nervous system lymphoma
tumour immune microenvironment
network analysis
chemotherapy
immunotherapy
url https://www.frontiersin.org/articles/10.3389/fgene.2022.921823/full
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