Journal Article

DKFZ-2018-02307

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png CD84 regulates PD-1/PD-L1 expression and function in chronic lymphocytic leukemia.

Lewinsky, H. ; Barak, A. F. ; Huber, V. ; Kramer, M. P. ; Radomir, L. ; Sever, L. ; Orr, I. ; Mirkin, V. ; Dezorella, N. ; Shapiro, M. ; Cohen, Y. ; Shvidel, L. ; Seiffert, M.DKFZ* ; Herishanu, Y. ; Becker-Herman, S. ; Shachar, I.

2018
ASCJ Ann Arbor, Mich.

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Please use a persistent id in citations: doi:10.1172/JCI96610

Abstract: Chronic lymphocytic leukemia (CLL) is characterized by clonal proliferation and progressive accumulation of mature B lymphocytes in the peripheral blood, lymphoid tissues, and bone marrow. CLL is characterized by profound immune defects leading to severe infectious complications. T cells are numerically, phenotypically, and functionally highly abnormal in CLL, with only limited ability to exert antitumor immune responses. Exhaustion of T cells has also been suggested to play an important role in antitumor responses. CLL-mediated T cell exhaustion is achieved by the aberrant expression of several inhibitory molecules on CLL cells and their microenvironment, prominently the programmed cell death ligand 1/programmed cell death 1 (PD-L1/PD-1) receptors. Previously, we showed that CD84, a member of the SLAM family of receptors, bridges between CLL cells and their microenvironment. In the current study, we followed CD84 regulation of T cell function. We showed that cell-cell interaction mediated through human and mouse CD84 upregulates PD-L1 expression on CLL cells and in their microenvironment and PD-1 expression on T cells. This resulted in suppression of T cell responses and activity in vitro and in vivo. Thus, our results demonstrate a role for CD84 in the regulation of immune checkpoints by leukemia cells and identify CD84 blockade as a therapeutic strategy to reverse tumor-induced immune suppression.

Note: #DKFZ-MOST-Ca166#

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Contributing Institute(s):

1. B060 Molekulare Genetik (B060)

Research Program(s):

1. 312 - Functional and structural genomics (POF3-312) (POF3-312)

Appears in the scientific report 2018

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Database coverage:
; BIOSIS Previews ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; IF >= 10 ; JCR ; NCBI Molecular Biology Database ; PubMed Central ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Web of Science Core Collection

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