دورية أكاديمية
Signaling via a CD27-TRAF2-SHP-1 axis during naive T cell activation promotes memory-associated gene regulatory networks.
| العنوان: | Signaling via a CD27-TRAF2-SHP-1 axis during naive T cell activation promotes memory-associated gene regulatory networks. |
|---|---|
| المؤلفون: | Jaeger-Ruckstuhl, Carla A.1 (AUTHOR) cjaeger@fredhutch.org, Lo, Yun1 (AUTHOR), Fulton, Elena1 (AUTHOR), Waltner, Olivia G.1 (AUTHOR), Shabaneh, Tamer B.1 (AUTHOR), Simon, Sylvain1 (AUTHOR), Muthuraman, Pranav V.1 (AUTHOR), Correnti, Colin E.1 (AUTHOR), Newsom, Oliver J.2 (AUTHOR), Engstrom, Ian A.2 (AUTHOR), Kanaan, Sami B.1 (AUTHOR), Bhise, Shruti S.1 (AUTHOR), Peralta, Jobelle M.C.1 (AUTHOR), Ruff, Raymond1,3 (AUTHOR), Price, Jason P.1,3 (AUTHOR), Stull, Sylvia M.1 (AUTHOR), Stevens, Andrew R.1 (AUTHOR), Bugos, Grace1 (AUTHOR), Kluesner, Mitchell G.2 (AUTHOR), Voillet, Valentin4 (AUTHOR) |
| المصدر: | Immunity (10747613). Feb2024, Vol. 57 Issue 2, p287-287. 1p. |
| مصطلحات موضوعية: | *GENE regulatory networks, *T cells, *TUMOR necrosis factor receptors, *CELL determination, *T cell receptors |
| مستخلص: | The interaction of the tumor necrosis factor receptor (TNFR) family member CD27 on naive CD8+ T (Tn) cells with homotrimeric CD70 on antigen-presenting cells (APCs) is necessary for T cell memory fate determination. Here, we examined CD27 signaling during Tn cell activation and differentiation. In conjunction with T cell receptor (TCR) stimulation, ligation of CD27 by a synthetic trimeric CD70 ligand triggered CD27 internalization and degradation, suggesting active regulation of this signaling axis. Internalized CD27 recruited the signaling adaptor TRAF2 and the phosphatase SHP-1, thereby modulating TCR and CD28 signals. CD27-mediated modulation of TCR signals promoted transcription factor circuits that induced memory rather than effector associated gene programs, which are induced by CD28 costimulation. CD27-costimulated chimeric antigen receptor (CAR)-engineered T cells exhibited improved tumor control compared with CD28-costimulated CAR-T cells. Thus, CD27 signaling during Tn cell activation promotes memory properties with relevance to T cell immunotherapy. [Display omitted] • CD27 is rapidly endocytosed in activated naive T cells after binding its ligand CD70 • CD27-TRAF2-SHP-1 modulates Lck phosphorylation in CD28-costimulated naive T cells • CD27 signaling promotes phenotypic and transcriptional adaptations of T cell memory • CAR-T cells generated with CD27 costimulation have superior antitumor efficacy Interaction of CD27 on naive T cells with CD70 on antigen-presenting cells is necessary for T cell memory fate determination. Jaeger-Ruckstuhl et al. engineer a trimeric CD70-ligand and assess consequences of CD27 ligation on receptor regulation, early proximal signaling, transcriptional and epigenetic states, revealing how modulation of T cell activation by CD27 affects fate commitment and efficacy of T cell immunotherapy. [ABSTRACT FROM AUTHOR] |
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In conjunction with T cell receptor (TCR) stimulation, ligation of CD27 by a synthetic trimeric CD70 ligand triggered CD27 internalization and degradation, suggesting active regulation of this signaling axis. Internalized CD27 recruited the signaling adaptor TRAF2 and the phosphatase SHP-1, thereby modulating TCR and CD28 signals. CD27-mediated modulation of TCR signals promoted transcription factor circuits that induced memory rather than effector associated gene programs, which are induced by CD28 costimulation. CD27-costimulated chimeric antigen receptor (CAR)-engineered T cells exhibited improved tumor control compared with CD28-costimulated CAR-T cells. Thus, CD27 signaling during Tn cell activation promotes memory properties with relevance to T cell immunotherapy. [Display omitted] • CD27 is rapidly endocytosed in activated naive T cells after binding its ligand CD70 • CD27-TRAF2-SHP-1 modulates Lck phosphorylation in CD28-costimulated naive T cells • CD27 signaling promotes phenotypic and transcriptional adaptations of T cell memory • CAR-T cells generated with CD27 costimulation have superior antitumor efficacy Interaction of CD27 on naive T cells with CD70 on antigen-presenting cells is necessary for T cell memory fate determination. Jaeger-Ruckstuhl et al. engineer a trimeric CD70-ligand and assess consequences of CD27 ligation on receptor regulation, early proximal signaling, transcriptional and epigenetic states, revealing how modulation of T cell activation by CD27 affects fate commitment and efficacy of T cell immunotherapy. [ABSTRACT FROM AUTHOR] ) |
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