Compromised anti-tumor–immune features of myeloid cell components in chronic myeloid leukemia patients

• Main Authors: Ibuki 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
• Format: Article
• Language: English
• Published: Nature Publishing Group 2021-09-01
• Series: Scientific Reports
• Online Access: https://doi.org/10.1038/s41598-021-97371-8

Abstract 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 “accelerator” (i.e., cDCs) but also applies the “brake” (i.e., monocytes and basophils) of anti-tumor immunity, compromising the defense against CML cells.