{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T22:51:05Z","timestamp":1791240665047,"version":"4.1.0"},"reference-count":52,"publisher":"Springer Science and Business Media LLC","issue":"7","license":[{"start":{"date-parts":[[2023,4,29]],"date-time":"2023-04-29T00:00:00Z","timestamp":1682726400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,4,29]],"date-time":"2023-04-29T00:00:00Z","timestamp":1682726400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Leukemia"],"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>To determine the overall tumor microenvironment (TME), characteristics, and transition mechanisms in primary central nervous system lymphoma (PCNSL), we performed spatial transcriptomics and matched the corresponding single-cell sequencing data of PCNSL patients. We found that tumor cells may achieve a \u201cTME remodeling pattern\u201d through an \u201cimmune pressure-sensing model\u201d, in which they could choose to reshape the TME into a barrier environment or a cold environment according to the immune pressure. A key <jats:italic>FKBP5<\/jats:italic><jats:sup><jats:italic>+<\/jats:italic><\/jats:sup> tumor subgroup was found to be responsible for pushing tumors into the barrier environment, which provides a possible way to evaluate the stage of PCNSL. The specific mechanism of the TME remodeling pattern and the key molecules of the immune pressure-sensing model were identified through the spatial communication analysis. Finally, we discovered the spatial and temporal distributions and variation characteristics of immune checkpoint molecules and CAR-T target molecules in immunotherapy. These data clarified the TME remodeling pattern of PCNSL, provided a reference for its immunotherapy, and provided suggestions for the TME remodeling mechanism of other cancers.<\/jats:p>","DOI":"10.1038\/s41375-023-01908-x","type":"journal-article","created":{"date-parts":[[2023,4,29]],"date-time":"2023-04-29T07:02:24Z","timestamp":1682751744000},"page":"1499-1510","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Spatial single cell analysis of tumor microenvironment remodeling pattern in primary central nervous system lymphoma"],"prefix":"10.1038","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7292-8903","authenticated-orcid":false,"given":"Yuan","family":"Xia","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8757-9737","authenticated-orcid":false,"given":"Tao","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guosheng","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingying","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongmei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuhua","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjing","family":"Ye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4438-1768","authenticated-orcid":false,"given":"Chunyan","family":"Ji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,4,29]]},"reference":[{"key":"1908_CR1","doi-asserted-by":"publisher","first-page":"4557","DOI":"10.1158\/0008-5472.CAN-18-3962","volume":"79","author":"DC Hinshaw","year":"2019","unstructured":"Hinshaw DC, Shevde LA. The tumor microenvironment innately modulates cancer progression. Cancer Res. 2019;79:4557\u201366.","journal-title":"Cancer Res"},{"key":"1908_CR2","doi-asserted-by":"publisher","first-page":"1014","DOI":"10.1038\/ni.2703","volume":"14","author":"TF Gajewski","year":"2013","unstructured":"Gajewski TF, Schreiber H, Fu YX. Innate and adaptive immune cells in the tumor microenvironment. Nat Immunol. 2013;14:1014\u201322.","journal-title":"Nat Immunol"},{"key":"1908_CR3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.immuni.2013.07.012","volume":"39","author":"S Chen Daniel","year":"2013","unstructured":"Chen Daniel S, Mellman I. Oncology meets immunology: The cancer-immunity cycle. Immunity 2013;39:1\u201310.","journal-title":"Immunity"},{"key":"1908_CR4","doi-asserted-by":"publisher","first-page":"855","DOI":"10.1016\/j.it.2016.09.006","volume":"37","author":"A Gardner","year":"2016","unstructured":"Gardner A, Ruffell B. Dendritic cells and cancer immunity. Trends Immunol. 2016;37:855\u201365.","journal-title":"Trends Immunol"},{"key":"1908_CR5","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1038\/s41573-018-0007-y","volume":"18","author":"J Galon","year":"2019","unstructured":"Galon J, Bruni D. Approaches to treat immune hot, altered and cold tumours with combination immunotherapies. Nat Rev Drug Discov. 2019;18:197\u2013218.","journal-title":"Nat Rev Drug Discov"},{"key":"1908_CR6","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.immuni.2013.07.008","volume":"39","author":"J Galon","year":"2013","unstructured":"Galon J, Angell HK, Bedognetti D, Marincola FM. The continuum of cancer immunosurveillance: Prognostic, predictive, and mechanistic signatures. Immunity 2013;39:11\u201326.","journal-title":"Immunity"},{"key":"1908_CR7","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1002\/path.4287","volume":"232","author":"J Galon","year":"2013","unstructured":"Galon J, Mlecnik B, Bindea G, Angell HK, Berger A, Lagorce C, et al. Towards the introduction of the \u2018Immunoscore\u2019 in the classification of malignant tumours. J Pathol. 2013;232:199\u2013209.","journal-title":"J Pathol"},{"key":"1908_CR8","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1016\/j.trecan.2020.02.022","volume":"6","author":"Q Duan","year":"2020","unstructured":"Duan Q, Zhang H, Zheng J, Zhang L. Turning cold into hot: Firing up the tumor microenvironment. Trend Cancer. 2020;6:605\u201318.","journal-title":"Trend Cancer"},{"key":"1908_CR9","doi-asserted-by":"publisher","first-page":"2410","DOI":"10.1200\/JCO.2017.72.7602","volume":"35","author":"C Grommes","year":"2017","unstructured":"Grommes C, DeAngelis LM. Primary CNS Lymphoma. J Clin Oncol. 2017;35:2410\u20138.","journal-title":"J Clin Oncol"},{"key":"1908_CR10","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1002\/hon.2598","volume":"37","author":"TT Batchelor","year":"2019","unstructured":"Batchelor TT. Primary central nervous system lymphoma: A curable disease. Hematol Oncol. 2019;37:15\u20138.","journal-title":"Hematol Oncol"},{"key":"1908_CR11","doi-asserted-by":"publisher","first-page":"971","DOI":"10.1182\/blood.2020008377","volume":"140","author":"LR Schaff","year":"2022","unstructured":"Schaff LR, Grommes C. Primary central nervous system lymphoma. Blood. 2022;140:971\u20139.","journal-title":"Blood"},{"key":"1908_CR12","doi-asserted-by":"publisher","first-page":"683007","DOI":"10.3389\/fonc.2021.683007","volume":"11","author":"B Wei","year":"2021","unstructured":"Wei B, Liu Z, Fan Y, Wang S, Dong C, Rao W, et al. Analysis of cellular heterogeneity in immune microenvironment of primary central nervous system lymphoma by single-cell sequencing. Front Oncol. 2021;11:683007.","journal-title":"Front Oncol"},{"key":"1908_CR13","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1038\/s41568-019-0224-7","volume":"20","author":"JH Sampson","year":"2020","unstructured":"Sampson JH, Gunn MD, Fecci PE, Ashley DM. Brain immunology and immunotherapy in brain tumours. Nat Rev Cancer. 2020;20:12\u201325.","journal-title":"Nat Rev Cancer"},{"key":"1908_CR14","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1016\/j.cell.2020.05.039","volume":"182","author":"AL Ji","year":"2020","unstructured":"Ji AL, Rubin AJ, Thrane K, Jiang S, Reynolds DL, Meyers RM, et al. Multimodal analysis of composition and spatial architecture in human squamous cell carcinoma. Cell 2020;182:497\u2013514.","journal-title":"Cell"},{"key":"1908_CR15","doi-asserted-by":"publisher","first-page":"3273","DOI":"10.1093\/bioinformatics\/btaa099","volume":"36","author":"EY Cao","year":"2020","unstructured":"Cao EY, Ouyang JF, Rackham OJL. GeneSwitches: ordering gene expression and functional events in single-cell experiments. Bioinformatics 2020;36:3273\u20135.","journal-title":"Bioinformatics"},{"key":"1908_CR16","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-21246-9","volume":"12","author":"S Jin","year":"2021","unstructured":"Jin S, Guerrero-Juarez CF, Zhang L, Chang I, Ramos R, Kuan CH, et al. Inference and analysis of cell-cell communication using CellChat. Nat Commun. 2021;12:1088.","journal-title":"Nat Commun"},{"key":"1908_CR17","doi-asserted-by":"publisher","first-page":"W98","DOI":"10.1093\/nar\/gkx247","volume":"45","author":"Z Tang","year":"2017","unstructured":"Tang Z, Li C, Kang B, Gao G, Li C, Zhang Z. GEPIA: A web server for cancer and normal gene expression profiling and interactive analyses. Nucleic Acids Res. 2017;45:W98\u2013W102.","journal-title":"Nucleic Acids Res"},{"key":"1908_CR18","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1146\/annurev-med-062315-120245","volume":"68","author":"K Newick","year":"2017","unstructured":"Newick K, O\u2019Brien S, Moon E, Albelda SM. CAR T cell therapy for solid tumors. Annu Rev Med. 2017;68:139\u201352.","journal-title":"Annu Rev Med"},{"key":"1908_CR19","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1007\/978-981-15-3266-5_3","volume":"1248","author":"L Ai","year":"2020","unstructured":"Ai L, Xu A, Xu J. Roles of PD-1\/PD-L1 pathway: Signaling, cancer, and beyond. Adv Exp Med Biol. 2020;1248:33\u201359.","journal-title":"Adv Exp Med Biol"},{"key":"1908_CR20","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1038\/nrc3239","volume":"12","author":"DM Pardoll","year":"2012","unstructured":"Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 2012;12:252\u201364.","journal-title":"Nat Rev Cancer"},{"key":"1908_CR21","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-022-01110-1","volume":"14","author":"M Heming","year":"2022","unstructured":"Heming M, Haessner S, Wolbert J, Lu IN, Li X, Brokinkel B, et al. Intratumor heterogeneity and T cell exhaustion in primary CNS lymphoma. Genome Med. 2022;14:109.","journal-title":"Genome Med."},{"key":"1908_CR22","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1038\/ni.3656","volume":"18","author":"RS Klein","year":"2017","unstructured":"Klein RS, Garber C, Howard N. Infectious immunity in the central nervous system and brain function. Nat Immunol. 2017;18:132\u201341.","journal-title":"Nat Immunol"},{"key":"1908_CR23","doi-asserted-by":"publisher","first-page":"4202","DOI":"10.1158\/1078-0432.CCR-18-1627","volume":"25","author":"W Tomaszewski","year":"2019","unstructured":"Tomaszewski W, Sanchez-Perez L, Gajewski TF, Sampson JH. Brain tumor microenvironment and host state: Implications for immunotherapy. Clin Cancer Res. 2019;25:4202\u201310.","journal-title":"Clin Cancer Res"},{"key":"1908_CR24","doi-asserted-by":"publisher","first-page":"736298","DOI":"10.3389\/fcell.2021.736298","volume":"9","author":"L Zhan","year":"2021","unstructured":"Zhan L, Zhang J, Zhu S, Liu X, Zhang J, Wang W, et al. N(6)-Methyladenosine RNA Modification: An emerging immunotherapeutic approach to turning up cold tumors. Front Cell Dev Biol. 2021;9:736298.","journal-title":"Front Cell Dev Biol"},{"key":"1908_CR25","doi-asserted-by":"publisher","first-page":"5365","DOI":"10.7150\/thno.58390","volume":"11","author":"YT Liu","year":"2021","unstructured":"Liu YT, Sun ZJ. Turning cold tumors into hot tumors by improving T-cell infiltration. Theranostics 2021;11:5365\u201386.","journal-title":"Theranostics"},{"key":"1908_CR26","first-page":"797","volume":"3","author":"LL van der Woude","year":"2017","unstructured":"van der Woude LL, Gorris MAJ, Halilovic A, Figdor CG, de Vries IJM. Migrating into the Tumor: A Roadmap for T Cells. Trends. Cancer 2017;3:797\u2013808.","journal-title":"Cancer"},{"key":"1908_CR27","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-021-03113-9","volume":"19","author":"I Schlam","year":"2021","unstructured":"Schlam I, Church SE, Hether TD, Chaldekas K, Hudson BM, White AM, et al. The tumor immune microenvironment of primary and metastatic HER2- positive breast cancers utilizing gene expression and spatial proteomic profiling. J Transl Med. 2021;19:480.","journal-title":"J Transl Med"},{"key":"1908_CR28","doi-asserted-by":"publisher","first-page":"113791","DOI":"10.1016\/j.addr.2021.05.001","volume":"175","author":"NSH Too","year":"2021","unstructured":"Too NSH, Ho NCW, Adine C, Iyer NG, Fong ELS. Hot or cold: Bioengineering immune contextures into in vitro patient-derived tumor models. Adv Drug Deliv Rev. 2021;175:113791.","journal-title":"Adv Drug Deliv Rev"},{"key":"1908_CR29","doi-asserted-by":"publisher","first-page":"163","DOI":"10.3389\/fonc.2019.00163","volume":"9","author":"L Sevenich","year":"2019","unstructured":"Sevenich L. Turning \u201cCold\u201d Into \u201cHot\u201d Tumors\u2014Opportunities and Challenges for Radio-Immunotherapy Against Primary and Metastatic Brain Cancers. Front Oncol. 2019;9:163.","journal-title":"Front Oncol"},{"key":"1908_CR30","doi-asserted-by":"publisher","first-page":"1119","DOI":"10.1073\/pnas.1904022116","volume":"117","author":"JH Newman","year":"2020","unstructured":"Newman JH, Chesson CB, Herzog NL, Bommareddy PK, Aspromonte SM, Pepe R, et al. Intratumoral injection of the seasonal flu shot converts immunologically cold tumors to hot and serves as an immunotherapy for cancer. Proc Natl Acad Sci USA. 2020;117:1119\u201328.","journal-title":"Proc Natl Acad Sci USA"},{"key":"1908_CR31","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1038\/s41392-022-00946-8","volume":"7","author":"X Pan","year":"2022","unstructured":"Pan X, Wang J, Guo L, Na F, Du J, Chen X, et al. Identifying a confused cell identity for esophageal squamous cell carcinoma. Signal Transduct Target Ther. 2022;7:122.","journal-title":"Signal Transduct Target Ther"},{"key":"1908_CR32","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-04724-5","volume":"9","author":"E Berglund","year":"2018","unstructured":"Berglund E, Maaskola J, Schultz N, Friedrich S, Marklund M, Bergenstrahle J, et al. Spatial maps of prostate cancer transcriptomes reveal an unexplored landscape of heterogeneity. Nat Commun. 2018;9:2419.","journal-title":"Nat Commun"},{"key":"1908_CR33","doi-asserted-by":"publisher","first-page":"1571","DOI":"10.6004\/jnccn.2020.7667","volume":"18","author":"M Holdhoff","year":"2020","unstructured":"Holdhoff M, Mrugala MM, Grommes C, Kaley TJ, Swinnen LJ, Perez-Heydrich C, et al. Challenges in the Treatment of Newly Diagnosed and Recurrent Primary Central Nervous System Lymphoma. J Natl Compr Canc Netw. 2020;18:1571\u20138.","journal-title":"J Natl Compr Canc Netw"},{"key":"1908_CR34","doi-asserted-by":"publisher","first-page":"100213","DOI":"10.1016\/j.esmoop.2021.100213","volume":"6","author":"T Calimeri","year":"2021","unstructured":"Calimeri T, Steffanoni S, Gagliardi F, Chiara A, Ferreri AJM. How we treat primary central nervous system lymphoma. ESMO Open. 2021;6:100213.","journal-title":"ESMO Open"},{"key":"1908_CR35","doi-asserted-by":"publisher","DOI":"10.1007\/s11912-021-01116-9","volume":"23","author":"KW Song","year":"2021","unstructured":"Song KW, Batchelor T. Treatment of Primary CNS Lymphoma: Maximizing Clinical Benefit, Minimizing Neurotoxicity. Curr Oncol Rep. 2021;23:132.","journal-title":"Curr Oncol Rep"},{"key":"1908_CR36","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1016\/j.ejca.2019.05.024","volume":"117","author":"C Soussain","year":"2019","unstructured":"Soussain C, Choquet S, Blonski M, Leclercq D, Houillier C, Rezai K, et al. Ibrutinib monotherapy for relapse or refractory primary CNS lymphoma and primary vitreoretinal lymphoma: Final analysis of the phase II \u2018proof-of-concept\u2019 iLOC study by the Lymphoma study association (LYSA) and the French oculo-cerebral lymphoma (LOC) network. Eur J Cancer. 2019;117:121\u201330.","journal-title":"Eur J Cancer"},{"key":"1908_CR37","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1186\/s13000-019-0833-1","volume":"14","author":"P Niparuck","year":"2019","unstructured":"Niparuck P, Boonsakan P, Sutthippingkiat T, Pukiat S, Chantrathammachart P, Phusanti S, et al. Treatment outcome and prognostic factors in PCNSL. Diagn Pathol. 2019;14:56.","journal-title":"Diagn Pathol"},{"key":"1908_CR38","doi-asserted-by":"publisher","first-page":"294","DOI":"10.1080\/08916934.2021.1925885","volume":"54","author":"Q Lu","year":"2021","unstructured":"Lu Q, Cai P, Yu Y, Liu Z, Chen G, Zeng Z. Sema4D correlates with tumour immune infiltration and is a prognostic biomarker in bladder cancer, renal clear cell carcinoma, melanoma and thymoma. Autoimmunity 2021;54:294\u2013302.","journal-title":"Autoimmunity"},{"key":"1908_CR39","doi-asserted-by":"publisher","first-page":"4098","DOI":"10.1245\/s10434-021-10111-0","volume":"28","author":"AJ Rossi","year":"2021","unstructured":"Rossi AJ, Khan TM, Hong H, Lesinski GB, Wu C, Hernandez JM. Pepinemab (Anti-SEMA4D) in Combination with Ipilimumab or Nivolumab for Patients with Resectable Pancreatic and Colorectal Cancer. Ann Surgical Oncol. 2021;28:4098\u20139.","journal-title":"Ann Surgical Oncol"},{"key":"1908_CR40","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1038\/nm.4441","volume":"24","author":"TJ Fry","year":"2018","unstructured":"Fry TJ, Shah NN, Orentas RJ, Stetler-Stevenson M, Yuan CM, Ramakrishna S, et al. CD22-targeted CAR T cells induce remission in B-ALL that is naive or resistant to CD19-targeted CAR immunotherapy. Nat Med. 2018;24:20\u20138.","journal-title":"Nat Med"},{"key":"1908_CR41","doi-asserted-by":"publisher","first-page":"6185","DOI":"10.1158\/1078-0432.CCR-18-0426","volume":"24","author":"G Enblad","year":"2018","unstructured":"Enblad G, Karlsson H, Gammelgard G, Wenthe J, Lovgren T, Amini RM, et al. A Phase I\/IIa Trial Using CD19-Targeted Third-Generation CAR T Cells for Lymphoma and Leukemia. Clin Cancer Res. 2018;24:6185\u201394.","journal-title":"Clin Cancer Res"},{"key":"1908_CR42","doi-asserted-by":"publisher","first-page":"2150","DOI":"10.3390\/ijms22042150","volume":"22","author":"M Martino","year":"2021","unstructured":"Martino M, Alati C, Canale FA, Musuraca G, Martinelli G, Cerchione C. A Review of Clinical Outcomes of CAR T-Cell Therapies for B-Acute Lymphoblastic Leukemia. Int J Mol Sci. 2021;22:2150.","journal-title":"Int J Mol Sci"},{"key":"1908_CR43","doi-asserted-by":"publisher","first-page":"e711","DOI":"10.1016\/S2352-3026(21)00238-6","volume":"8","author":"AB Leahy","year":"2021","unstructured":"Leahy AB, Newman H, Li Y, Liu H, Myers R, DiNofia A, et al. CD19-targeted chimeric antigen receptor T-cell therapy for CNS relapsed or refractory acute lymphocytic leukaemia: a post-hoc analysis of pooled data from five clinical trials. Lancet Haematol. 2021;8:e711\u2013e22.","journal-title":"Lancet Haematol"},{"key":"1908_CR44","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1002\/cpt.1674","volume":"107","author":"SA Holstein","year":"2019","unstructured":"Holstein SA, Lunning MA. CAR T\u2010Cell Therapy in Hematologic Malignancies: A Voyage in Progress. Clin Pharmacol Therapeutics. 2019;107:112\u201322.","journal-title":"Clin Pharmacol Therapeutics"},{"key":"1908_CR45","doi-asserted-by":"publisher","first-page":"2320","DOI":"10.1016\/j.ymthe.2020.09.015","volume":"28","author":"J Wagner","year":"2020","unstructured":"Wagner J, Wickman E, DeRenzo C, Gottschalk S. CAR T Cell Therapy for Solid Tumors: Bright Future or Dark Reality? Mol Ther. 2020;28:2320\u201339.","journal-title":"Mol Ther"},{"key":"1908_CR46","doi-asserted-by":"publisher","first-page":"697","DOI":"10.3389\/fonc.2020.00697","volume":"10","author":"S Mardiana","year":"2020","unstructured":"Mardiana S, Gill S. CAR T Cells for Acute Myeloid Leukemia: State of the Art and Future Directions. Front Oncol. 2020;10:697.","journal-title":"Front Oncol"},{"key":"1908_CR47","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1186\/s13045-021-01178-z","volume":"14","author":"J Shi","year":"2021","unstructured":"Shi J, Zhang Z, Cen H, Wu H, Zhang S, Liu J, et al. CAR T cells targeting CD99 as an approach to eradicate T-cell acute lymphoblastic leukemia without normal blood cells toxicity. J Hematol Oncol. 2021;14:162.","journal-title":"J Hematol Oncol"},{"key":"1908_CR48","doi-asserted-by":"publisher","first-page":"3073","DOI":"10.3390\/cancers13123073","volume":"13","author":"HG Wirsching","year":"2021","unstructured":"Wirsching HG, Weller M, Balabanov S, Roth P. Targeted Therapies and Immune Checkpoint Inhibitors in Primary CNS Lymphoma. Cancers (Basel). 2021;13:3073.","journal-title":"Cancers (Basel)"},{"key":"1908_CR49","first-page":"491","volume":"11","author":"A Monabati","year":"2020","unstructured":"Monabati A, Nematollahi P, Dehghanian A, Safaei A, Sadeghipour A, Movahedinia S, et al. Immune checkpoint molecules in primary diffuse large B-Cell lymphoma of the central nervous system. Basic Clin Neurosci J. 2020;11:491\u20138.","journal-title":"Basic Clin Neurosci J"},{"key":"1908_CR50","doi-asserted-by":"publisher","first-page":"303","DOI":"10.21147\/j.issn.1000-9604.2020.03.03","volume":"32","author":"N Lin","year":"2020","unstructured":"Lin N, Song Y, Zhu J. Immune checkpoint inhibitors in malignant lymphoma: Advances and perspectives. Chin J Cancer Res. 2020;32:303\u201318.","journal-title":"Chin J Cancer Res"},{"key":"1908_CR51","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1080\/0284186X.2021.1881161","volume":"60","author":"M Abdulla","year":"2021","unstructured":"Abdulla M, Alexsson A, Sundstrom C, Ladenvall C, Mansouri L, Lindskog C, et al. PD-L1 and IDO1 are potential targets for treatment in patients with primary diffuse large B-cell lymphoma of the CNS. Acta Oncol. 2021;60:531\u20138.","journal-title":"Acta Oncol"},{"key":"1908_CR52","doi-asserted-by":"publisher","first-page":"95","DOI":"10.3960\/jslrt.18001","volume":"58","author":"Y Miyasato","year":"2018","unstructured":"Miyasato Y, Takashima Y, Takeya H, Yano H, Hayano A, Nakagawa T, et al. The expression of PD-1 ligands and IDO1 by macrophage\/microglia in primary central nervous system lymphoma. J Clin Exp Hematop. 2018;58:95\u2013101.","journal-title":"J Clin Exp Hematop"}],"container-title":["Leukemia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41375-023-01908-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41375-023-01908-x","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41375-023-01908-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,3]],"date-time":"2023-07-03T14:02:47Z","timestamp":1688392967000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41375-023-01908-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,29]]},"references-count":52,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2023,7]]}},"alternative-id":["1908"],"URL":"https:\/\/doi.org\/10.1038\/s41375-023-01908-x","relation":{},"ISSN":["0887-6924","1476-5551"],"issn-type":[{"value":"0887-6924","type":"print"},{"value":"1476-5551","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,29]]},"assertion":[{"value":"11 February 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 April 2023","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 April 2023","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 April 2023","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"The clinical PSNSL specimens were conducted with permission from the Ethics Committee of Qilu Hospital, Jinan, China. All patient tissue sections of PCNSL used in the study were obtained from the Pathology Department of Qilu Hospital, and all patients signed informed consent forms before sampling.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}]}}