期刊
FRONTIERS IN IMMUNOLOGY
卷 10, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2019.02085
关键词
NK cell; follicular lymphoma (FL); rituximab; killer cell immunoglobin-like receptor; ki67
类别
资金
- Swedish Research Council
- Swedish Children's Cancer Society
- Swedish Cancer Society
- Tobias Foundation
- Karolinska Institutet
- Wenner-Gren Foundation
- Norwegian Cancer Society
- Norwegian Research Council
- South-Eastern Norway Regional Health Authority
- KG Jebsen Center for Cancer Immunotherapy
- BBSRC [BB/N01524X/1]
- Dr. Mildred Scheel Foundation for Cancer Research of the German Cancer Aid Organization
- BBSRC [BB/N01524X/1] Funding Source: UKRI
Monotherapy with the anti-CD20 monoclonal antibody rituximab can induce complete responses (CR) in patients with follicular lymphoma (FL). Resting FcR gamma III+ (CD16(+)) natural killer (NK) cells respond strongly to rituximab-coated target cells in vitro. Yet, the contribution of NK cells in the therapeutic effect in vivo remains unknown. Here, we followed the NK cell repertoire dynamics in the lymph node and systemically during rituximab monotherapy in patients with FL. At baseline, NK cells in the tumor lymph node had a naive phenotype albeit they were more differentiated than NK cells derived from control tonsils as determined by the frequency of CD56(dim) NK cells and the expression of killer cell immunoglobulin-like receptors (KIR), CD57 and CD16. Rituximab therapy induced a rapid drop in NK cell numbers coinciding with a relative increase in the frequency of Ki67(+) NK cells both in the lymph node and peripheral blood. The Ki67(+) NK cells had slightly increased expression of CD16, CD57 and higher levels of granzyme A and perforin. The in vivo activation of NK cells was paralleled by a temporary loss of in vitro functionality, primarily manifested as decreased IFN gamma production in response to rituximab-coated targets. However, patients with pre-existing NKG2C(+) adaptive NK cell subsets showed less Ki67 upregulation and were refractory to the loss of functionality. These data reveal variable imprints of rituximab monotherapy on the NK cell repertoire, which may depend on pre-existing repertoire diversity.
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