Ontology type: schema:ScholarlyArticle Open Access: True
2021-09-10
AUTHORSIbuki Harada, Haruka Sasaki, Koichi Murakami, Akira Nishiyama, Jun Nakabayashi, Motohide Ichino, Takuya Miyazaki, Ken Kumagai, Kenji Matsumoto, Maki Hagihara, Wataru Kawase, Takayoshi Tachibana, Masatsugu Tanaka, Tomoyuki Saito, Heiwa Kanamori, Hiroyuki Fujita, Shin Fujisawa, Hideaki Nakajima, Tomohiko Tamura
ABSTRACTChronic myeloid leukemia (CML) is a form of myeloproliferative neoplasm caused by the oncogenic tyrosine kinase BCR-ABL. Although tyrosine kinase inhibitors have dramatically improved the prognosis of patients with CML, several problems such as resistance and recurrence still exist. Immunological control may contribute to solving these problems, and it is important to understand why CML patients fail to spontaneously develop anti-tumor immunity. Here, we show that differentiation of conventional dendritic cells (cDCs), which are vital for anti-tumor immunity, is restricted from an early stage of hematopoiesis in CML. In addition, we found that monocytes and basophils, which are increased in CML patients, express high levels of PD-L1, an immune checkpoint molecule that inhibits T cell responses. Moreover, RNA-sequencing analysis revealed that basophils express genes related to poor prognosis in CML. Our data suggest that BCR-ABL not only disrupts the “accelerator” (i.e., cDCs) but also applies the “brake” (i.e., monocytes and basophils) of anti-tumor immunity, compromising the defense against CML cells. More... »
PAGES18046
http://scigraph.springernature.com/pub.10.1038/s41598-021-97371-8
DOIhttp://dx.doi.org/10.1038/s41598-021-97371-8
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PUBMEDhttps://www.ncbi.nlm.nih.gov/pubmed/34508131
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"description": "Chronic myeloid leukemia (CML) is a form of myeloproliferative neoplasm caused by the oncogenic tyrosine kinase BCR-ABL. Although tyrosine kinase inhibitors have dramatically improved the prognosis of patients with CML, several problems such as resistance and recurrence still exist. Immunological control may contribute to solving these problems, and it is important to understand why CML patients fail to spontaneously develop anti-tumor immunity. Here, we show that differentiation of conventional dendritic cells (cDCs), which are vital for anti-tumor immunity, is restricted from an early stage of hematopoiesis in CML. In addition, we found that monocytes and basophils, which are increased in CML patients, express high levels of PD-L1, an immune checkpoint molecule that inhibits T cell responses. Moreover, RNA-sequencing analysis revealed that basophils express genes related to poor prognosis in CML. Our data suggest that BCR-ABL not only disrupts the \u201caccelerator\u201d (i.e., cDCs) but also applies the \u201cbrake\u201d (i.e., monocytes and basophils) of anti-tumor immunity, compromising the defense against CML cells.",
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"id": "sg:journal.1045337",
"issn": [
"2045-2322"
],
"name": "Scientific Reports",
"publisher": "Springer Nature",
"type": "Periodical"
},
{
"issueNumber": "1",
"type": "PublicationIssue"
},
{
"type": "PublicationVolume",
"volumeNumber": "11"
}
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"keywords": [
"chronic myeloid leukemia",
"anti-tumor immunity",
"conventional dendritic cells",
"CML patients",
"BCR-ABL",
"chronic myeloid leukemia patients",
"prognosis of patients",
"immune checkpoint molecules",
"T cell responses",
"myeloid leukemia patients",
"oncogenic tyrosine kinase BCR-ABL",
"tyrosine kinase inhibitors",
"tyrosine kinase BCR-ABL",
"checkpoint molecules",
"dendritic cells",
"PD-L1",
"poor prognosis",
"myeloid leukemia",
"immunological control",
"leukemia patients",
"immune features",
"CML cells",
"myeloproliferative neoplasms",
"patients",
"cell responses",
"kinase inhibitors",
"immunity",
"prognosis",
"cell components",
"early stages",
"high levels",
"cells",
"recurrence",
"neoplasms",
"leukemia",
"monocytes",
"basophils",
"inhibitors",
"hematopoiesis",
"response",
"differentiation",
"RNA",
"levels",
"control",
"genes",
"resistance",
"defense",
"stage",
"addition",
"data",
"analysis",
"features",
"molecules",
"components",
"form",
"problem",
"brake",
"accelerator"
],
"name": "Compromised anti-tumor\u2013immune features of myeloid cell components in chronic myeloid leukemia patients",
"pagination": "18046",
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