期刊
CANCERS
卷 14, 期 1, 页码 -出版社
MDPI
DOI: 10.3390/cancers14010016
关键词
Nurse-like cells; polarization; survival; CLL; IL-10; TNF
类别
资金
- Janssen Foundation
- Inserm
- CNRS
- Toulouse III University
In chronic lymphocytic leukemia, M2-like nurse-like cells (NLC) provide protection against apoptosis for leukemic cells through the release of IL-10, while M1-like NLC do not have this effect. The balance between IL-10 and TNF plays an important role in maintaining the protective phenotype of NLCs and the survival of CLL cells.
Simple Summary In in vitro co-cultures of CLL cells and nurse-like cells (NLC), protection against apoptosis is only provided by M2-like NLC, and not M1-like NLC. In this study, we propose that fine-tuning of NLC polarization (and therefore survival of leukemic cells) is dictated by a balance between IL-10 and TNF. Tumor-associated macrophages (TAMs) in chronic lymphocytic leukemia (CLL) are also called nurse-like cells (NLC), and confer survival signals through the release of soluble factors and cellular contacts. While in most patient samples the presence of NLC in co-cultures guarantees high viability of leukemic cells in vitro, in some cases this protective effect is absent. These macrophages are characterized by an M1-like phenotype. We show here that their reprogramming towards an M2-like phenotype (tumor-supportive) with IL-10 leads to an increase in leukemic cell survival. Inflammatory cytokines, such as TNF, are also able to depolarize M2-type protective NLC (decreasing CLL cell viability), an effect which is countered by IL-10 or blocking antibodies. Interestingly, both IL-10 and TNF are implied in the pathophysiology of CLL and their elevated level is associated with bad prognosis. We propose that the molecular balance between these two cytokines in CLL niches plays an important role in the maintenance of the protective phenotype of NLCs, and therefore in the survival of CLL cells.
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