Signalling via CD70, a member of the TNF family, regulates T cell functions

  title={Signalling via CD70, a member of the TNF family, regulates T cell functions},
  author={Pilar Garc{\'i}a and A Heredia and Teresa Bell{\'o}n and Emilio Carpio and Manuel Llano and Esther Caparr{\'o}s and Pedro Aparicio and Miguel L{\'o}pez-Botet},
  journal={Journal of Leukocyte Biology},
In the present work, we provide data supporting that CD70, a tumor necrosis factor (TNF)‐related molecule, defined as the CD27 ligand (CD27L), may actively regulate T cell functions similarly to other members of the TNF family (i.e., CD40L and CD30L). Cross‐linking CD70 with specific monoclonal antibodies (mAb) stimulated cytotoxicity and cytokine production in human T cell clones. Detection of intracellular‐free calcium mobilization and mitogen‐activated protein kinase phosphorylation upon mAb… 
CD27 and CD70 in T cell and B cell activation.
Therapeutic targeting of CD70 and CD27
  • H. Wajant
  • Biology
    Expert opinion on therapeutic targets
  • 2016
This review is focused on strategies and concepts that exploit the function and expression pattern of these molecules for therapeutic purposes and identifies biomarkers and stratification concepts that fit optimally to the dominant function(s) of CD70 and CD27 in the corresponding individual case.
Timing and tuning of CD27–CD70 interactions: the impact of signal strength in setting the balance between adaptive responses and immunopathology
It is concluded that optimal tuning of CD27–CD70 interaction is crucial for the regulation of the cellular immune response and that these receptors do not have a unique function per se but that rather the timing, context, and intensity of these costimulatory signals determine the functional consequence of their activity.
Melanoma-expressed CD70 is involved in invasion and metastasis
A new non-immunological function of melanoma-expressed CD70 is described, which involves melanoma invasiveness through MAPK pathway activation, RhoE overexpression, ROCK1 and MYPT1 phosphorylation decrease, and stress fibres and focal adhesions disappearance.
CD70 Inversely Regulates Tregs and iNKT Cells and Modulates Type 1 Diabetes in NOD Mice
The data demonstrates that CD70 ablation alters thymocyte selection and increases circulating T cell levels, and demonstrates that the CD27-CD70 costimulatory pathway regulates the differentiation program of multiple T cell subsets involved in T1D development, and may be subject to therapeutic targeting.
The costimulatory molecule CD70 is regulated by distinct molecular mechanisms and is associated with overall survival in diffuse large B‐cell lymphoma
CD70 is targeted by recurrent deletions, somatic mutations and promoter hypermethylation, but its high level of expression is related to an unfavorable outcome, indicating that this molecule may constitute a potential therapeutic target in selected DLBCL.
Endoplasmic Reticulum Stress-Mediated Apoptosis of EBV-Transformed B Cells by Cross-Linking of CD70 Is Dependent upon Generation of Reactive Oxygen Species and Activation of p38 MAPK and JNK Pathway
Cross-linking of CD70 on EBV-transformed B cells triggered ER stress-mediated apoptosis via ROS generation and JNK and p38 MAPK pathway activation and provides data supporting CD70 as a viable target for an Ab-based therapy againstEBV-related tumors.
Expression of CD70 in nasal natural killer/T cell lymphoma cell lines and patients; its role for cell proliferation through binding to soluble CD27
It is suggested that CD70 acts as a functional receptor binding to soluble CD27, resulting in lymphoma progression and that immunotherapy using anti‐CD70 antibody may be a potential candidate for treatment for NNKTL.
Mycophenolic Acid‐Mediated Suppression of Human CD4+ T Cells: More Than Mere Guanine Nucleotide Deprivation
  • X. HeR. Smeets I. Joosten
  • Biology
    American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
  • 2011
Novel insights are presented into the mechanisms underlying mycophenolic acid‐mediated suppression of human CD4+ T cells and an anti‐CD70 agonist was found to restore both STAT5 and Akt/mTOR signaling and may thereby prevent apoptosis and promote survival.


Engagement of CD27 with its ligand CD70 provides a second signal for T cell activation.
It is demonstrated here that interaction of CD27 with its ligand provides a potent second signal for cytokine production, induction of activation Ags, and proliferation of unprimed CD45RA+, and to a lesser extent, of primed CD45R0+ peripheral blood T cells.
Characterization of the human CD27 ligand, a novel member of the TNF gene family.
CD27 and its ligand are identified as potentially important structures involved in cellular interactions between T and B lymphocytes and exerted a potent inhibitory effect on the proliferation of T cells in response to allogeneic B cells and PHA.
Reverse signaling via CD30 ligand.
Results indicate that cross-linked CD30L can transduce a signal to the ligand-bearing cell, suggesting that, as a rule, TNF family members and their cognate receptors signal bidirectionally, blurring the distinction between ligand and receptor.
Characterization of murine CD70, the ligand of the TNF receptor family member CD27.
MCD70 transcript levels are strongly but transiently up-regulated during lymphocyte activation, which is in line with a role for the CD27-CD70 receptor pair early in the immune response, and recombinant mCD70 potently costimulates T cell proliferation.
Novel mAbs reveal potent co-stimulatory activity of murine CD27.
Upon cross-linking, anti-CD27 mAb amplified the proliferative response of purified T lymphocytes to suboptimal stimulation with concanavalin A at least 4-fold, indicating that such mAbs can mimick ligand binding and demonstrates that CD27 also acts as a potent co-stimulatory molecule in the murine system.
Characterization of murine CD70 by molecular cloning and mAb.
Results suggest a contribution of CD70 to murine T-B cognate interaction as proposed in the human system, and generate cDNA transfectants and anti-mCD70 mAb (FR70), which inhibited binding of a murine CD27-Fc fusion protein to mCD70 transfectant.
Expression of the Murine CD27 Ligand CD70 In Vitro and In Vivo4
The interaction between TNFR family member CD27 and its ligand CD70 promotes lymphocyte expansion and effector cell formation. In humans, control of CD27 function is partly regulated by the
Aberrant expression and reverse signalling of CD70 on malignant B cells
In a subset of malignant B cells CD70 can operate as receptor and as such might contribute to progression of these B‐cell malignancies.