Author:
Harada Ibuki,Sasaki Haruka,Murakami Koichi,Nishiyama Akira,Nakabayashi Jun,Ichino Motohide,Miyazaki Takuya,Kumagai Ken,Matsumoto Kenji,Hagihara Maki,Kawase Wataru,Tachibana Takayoshi,Tanaka Masatsugu,Saito Tomoyuki,Kanamori Heiwa,Fujita Hiroyuki,Fujisawa Shin,Nakajima Hideaki,Tamura Tomohiko
Abstract
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.
Funder
KAKENHI grants-in-aid from the Japan Society for the Promotion of Science
Fund for Creation of Innovation Centers for Advanced Interdisciplinary Research Areas Program from the Ministry of Education, Culture, Sports, Science and Technology
Grant from the Uehara Memorial Foundation
Grant for Strategic Research Promotion from Yokohama City University
Publisher
Springer Science and Business Media LLC
Cited by
5 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献