The CD47‐SIRPα signaling axis as an innate immune checkpoint in cancer

@article{Matlung2017TheCS,
  title={The CD47‐SIRP$\alpha$ signaling axis as an innate immune checkpoint in cancer},
  author={Hanke L. Matlung and Katka Szilagyi and Neil Barclay and Timo K. Van Den Berg},
  journal={Immunological Reviews},
  year={2017},
  volume={276},
  pages={145 - 164}
}
Immune checkpoint inhibitors, including those targeting CTLA‐4/B7 and the PD‐1/PD‐L1 inhibitory pathways, are now available for clinical use in cancer patients, with other interesting checkpoint inhibitors being currently in development. Most of these have the purpose to promote adaptive T cell‐mediated immunity against cancer. Here, we review another checkpoint acting to potentiate the activity of innate immune cells towards cancer. This innate immune checkpoint is composed of what has become… 
The MHC class I‐LILRB1 signalling axis as a promising target in cancer therapy
TLDR
Investigating the mechanisms underlying this immunosuppressive MHC class I‐LILRB1 signalling axis in tumour‐associated macrophages will be useful in developing therapies to restore macrophage function and control MHCclass I signalling in patient tumours will identify new therapeutic targets for the development of pharmaceutical‐based tumour immunotherapy.
Therapeutic modulation of the CD47-SIRPα axis in the pediatric tumor microenvironment: working up an appetite
TLDR
The aim of this review is to highlight the current literature and research on CD47, provide an impetus for investigation of its blockade in pediatric cancer histologies, and provide a rationale for new combination therapies in these patients.
Insights into CD47/SIRPα axis-targeting tumor immunotherapy
TLDR
The current knowledge about developing CD47/SIRPα checkpoint inhibitors is reviewed, avoiding potential side effect and designing optimal combination therapies are reviewed, and the key points for future clinical applications of CD 47/SirPα axis-targeted tumor immunotherapy are highlighted.
Cancer Therapy Targeting CD47/SIRPα
TLDR
The role of CD47/SIRPα axis in cancer, and the literature on the efficacy and safety of therapeutics targeting CD47 or SIRP α are reviewed, are summarized and the future implementation of these therapeutics in the treatments of various cancer types are discussed.
CD47‐signal regulatory protein α signaling system and its application to cancer immunotherapy
TLDR
Targeting of the CD47‐SIRPα signaling system is a promising strategy for cancer treatment based on modulation of both innate and acquired immune responses to tumor cells.
Advances in Anti-Tumor Treatments Targeting the CD47/SIRPα Axis
TLDR
The structure and function of CD47 are described, an overview of studies that have aimed to inhibitCD47-dependent avoidance of macrophage-mediated phagocytosis by tumor cells are provided, and the potential and challenges for targeting the CD47-SIRPα signaling pathway in anti-cancer therapy are assessed.
“Eating” Cancer cells by blocking CD47 signaling: Cancer therapy by targeting the innate immune checkpoint
TLDR
The CD47 and signal regulatory protein α (SIRPα) axis is emerging as a novel innate immune checkpoint of the immune cells of myeloid lineage and a balance should be established between the dual signals.
Preclinical characterization of the novel anti-SIRPα antibody BR105 that targets the myeloid immune checkpoint
TLDR
In vitro functional assays demonstrated that BR105 synergizes with therapeutic antibodies to promote phagocytosis of tumor cells and the combination of BR105 and therapeutic antibody significantly inhibits tumor growth in a xenograft tumor model.
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 184 REFERENCES
Cd47-Sirpα interaction and IL-10 constrain inflammation-induced macrophage phagocytosis of healthy self-cells
TLDR
The present study reveals that macrophage phagocytosis toward healthy self-cells is controlled by a two-tier mechanism: a forefront activation mechanism requiring the inflammatory cytokine-stimulated protein kinase C (PKC)-spleen tyrosine kinase (Syk) pathway, and the subsequent self-target discrimination mechanism controlled by the CD47-signal regulatory protein α (SIRPα)–mediated inhibition.
Inhibition of SIRPα in dendritic cells potentiates potent antitumor immunity
TLDR
SIRPα is a critical regulator of DC lifespan and activity, and its inhibition might improve the clinical efficacy of DC-based tumor vaccines.
CD47 in the Immune Response: Role of Thrombospondin and SIRP-α Reverse Signaling
TLDR
It is proposed that deletion of the CD47 gene in mice largely agrees with the in vitro data with human cells and the well-conserved tissue distribution of CD47 and SIRP-α across species may facilitate the transition from bench to bedside and maintain homeostasis and regulate innate and adaptive immune responses.
CD47–signal regulatory protein-α (SIRPα) interactions form a barrier for antibody-mediated tumor cell destruction
TLDR
It is shown that antibody-mediated killing of tumor cells is limited by a mechanism involving the interaction between tumor cell-expressed CD47 and the inhibitory receptor signal regulatory protein-α (SIRPα) on myeloid cells.
CD47 in the immune response: role of thrombospondin and SIRP-alpha reverse signaling.
TLDR
It is proposed that deletion of the CD47 gene in mice largely agrees with the in vitro data with human cells and the well-conserved tissue distribution of CD47 and SIRP-alpha across species may facilitate the transition from bench to bedside and maintain homeostasis and regulate innate and adaptive immune responses.
Targeting SIRP‐α protects from type 2‐driven allergic airway inflammation
TLDR
It is shown that early administration of a CD47‐Fc fusion molecule suppressed the accumulation of SIRP‐α+ DC in mediastinal LN, the development of systemic and local Th2 responses as well as airway inflammation in sensitized and challenged BALB/c mice.
MYC regulates the antitumor immune response through CD47 and PD-L1
TLDR
MYC regulates the expression of two immune checkpoint proteins on the tumor cell surface: the innate immune regulator CD47 (cluster of differentiation 47) and the adaptive immune checkpoint PD-L1 (programmed death–ligand 1).
Durable antitumor responses to CD47 blockade require adaptive immune stimulation
TLDR
It is shown that CD47 blockade alone or in combination with a tumor-specific antibody fails to generate antitumor immunity against syngeneic B16F10 tumors in mice, and synergistic activity is found, suggesting a role for both innate and adaptive inhibitory pathways in the response to therapeutic antibodies.
Engineered SIRPα Variants as Immunotherapeutic Adjuvants to Anticancer Antibodies
TLDR
This work modified the binding domain of human SIRPα, the receptor for CD47, for use as a CD47 antagonist, providing a universal method for augmenting the efficacy of therapeutic anticancer antibodies.
CD47 Blockade Triggers T cell-mediated Destruction of Immunogenic Tumors
TLDR
It is revealed that the therapeutic effects of CD47 blockade depend on dendritic cell but not macrophage cross-priming of T cell responses, suggesting that T cell–mediated elimination of immunogenic tumors is driven by anti-CD47 treatment, further bridging the innate and adaptive responses.
...
1
2
3
4
5
...