The role of CD47-SIRPα immune checkpoint in tumor immune evasion and innate immunotherapy

Li, Zihao; Li, Yue; Gao, Jing; Fu, Ying; Hua, Peiyan; Jing, Yingying; Cai, Mingjun; Wang, Hongda; Tong, Ti

doi:10.1016/j.lfs.2021.119150

Cited by 49 publications

(45 citation statements)

References 170 publications

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“…In recent years, pre-clinical studies on the concept of tumor microenvironment (TME) have revealed a variety of immune cells interacting with each other and, respectively, regulating tumorigenesis or immune regulation. Research results showed that CD47-SIRPα immune checkpoint pathway played important roles in tumor immune evasion and innate immunotherapy [ 31 ]. The expression of CD47 also has an important impact on the construction of TME [ 32 ], whereas CD47 deficiency led to cancer stem cell depletion.…”

Section: Sirpα-cd47 Signal Pathwaymentioning

confidence: 99%

“…A potential explanation for the differential binding of CD47 mAbs to different cells could be due to the fact that CD47 associates with different membrane proteins (in cis ) on different cells. Therefore, certain epitopes may be masked by CD47 binding partners in different cells (such as erythrocyte membrane protein 4.2 and/or Rh complex components [ 37 ]), or dependent on CD47 interacting proteins (such as integrin [ 31 ]), or physically associated with other membrane proteins (such as VEGFR2) [ 31 ]. Because CD47 can be heavily glycosylated with five potential NXT/S sequences in its extracellular IgV domain [ 38 ] and/or modified by addition of glycosaminoglycans, differing patterns or extents of carbohydrate additions in different cell types could also explain the differential binding of CD47 antibodies [ 39 ].…”

Section: Sirpα-cd47 Signal Pathwaymentioning

confidence: 99%

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Targeting CD47 for cancer immunotherapy

et al. 2021

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Much progress has been made in targeting CD47 for cancer immunotherapy in solid tumors (ST) and hematological malignancies. We summarized the CD47-related clinical research and analyzed the research trend both in the USA and in China. As of August 28, 2021, there are a total 23 related therapeutic agents with 46 clinical trials in the NCT registry platform. Among these trials, 29 are in ST, 14 in hematological malignancies and 3 in both solid tumor and hematological malignancy. The ST include gastric cancer, head and neck squamous cell carcinoma and leiomyosarcoma, while the hematological malignancies include non-Hodgkin's lymphoma, acute myeloid leukemia, myelodysplastic syndrome, multiple myeloma and chronic myeloid leukemia. Majority of the CD47-related clinical trials are at the early phases, such as 31 at phase I, 14 at phase II and 1 at phase III in the USA and 9, 6, 1, in China, respectively. The targets and spectrums of mechanism of action include 26 with mono-specific and 20 with bi-specific targets in the USA and 13 with mono-specific and 3 with bi-specific targets in China. The new generation CD47 antibodies have demonstrated promising results, and it is highly hopeful that some candidate agents will emerge and make into clinical application to meet the urgent needs of patients.

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Section: Sirpα-cd47 Signal Pathwaymentioning

confidence: 99%

Section: Sirpα-cd47 Signal Pathwaymentioning

confidence: 99%

Targeting CD47 for cancer immunotherapy

et al. 2021

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“…The CD47-SIRPα signaling system is a cell-cell communication system ( Zhang H. et al, 2015 ; Matlung et al, 2017 ; Weiskopf, 2017 ). CD47-SIRPα interactions have been termed an innate immune checkpoint in macrophages ( Li et al, 2021 ). Blockade of anti-phagocytic CD47-SIRPα interactions using humanized antibodies to CD47 (Hu5F9-G4) has yielded promising results in preclinical studies of a number of human malignancies including pediatric brain tumors: medulloblastoma, atypical teratoid rhabdoid tumors, primitive neuroectodermal tumor, pediatric glioblastoma, and diffuse intrinsic pontine glioma ( Gholamin et al, 2017 ) and accelerates the clearance of hematomas in experimental intraventricular hemorrhage ( Ye et al, 2021 ).…”

Section: The Small Neural Proteoglycansmentioning

confidence: 99%

“…Deficient levels of HA in PNN structures promote epilepsy and spontaneous convulsions in animal models (Perkins et al, 2017). The CS-PGs of PNNs have important functional roles to play in perisynaptic structures that prevent the development Zhang H. et al, 2015;Matlung et al, 2017;Bedoui et al, 2018;Hutter et al, 2019;Li et al, 2021…”

Section: Roles For the Cs-rich Lectican Pg Family In Perineuronal Net Structuresmentioning

confidence: 99%

Neural Tissue Homeostasis and Repair Is Regulated via CS and DS Proteoglycan Motifs

Hayes

Melrose

2021

Front. Cell Dev. Biol.

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Chondroitin sulfate (CS) is the most abundant and widely distributed glycosaminoglycan (GAG) in the human body. As a component of proteoglycans (PGs) it has numerous roles in matrix stabilization and cellular regulation. This chapter highlights the roles of CS and CS-PGs in the central and peripheral nervous systems (CNS/PNS). CS has specific cell regulatory roles that control tissue function and homeostasis. The CNS/PNS contains a diverse range of CS-PGs which direct the development of embryonic neural axonal networks, and the responses of neural cell populations in mature tissues to traumatic injury. Following brain trauma and spinal cord injury, a stabilizing CS-PG-rich scar tissue is laid down at the defect site to protect neural tissues, which are amongst the softest tissues of the human body. Unfortunately, the CS concentrated in gliotic scars also inhibits neural outgrowth and functional recovery. CS has well known inhibitory properties over neural behavior, and animal models of CNS/PNS injury have demonstrated that selective degradation of CS using chondroitinase improves neuronal functional recovery. CS-PGs are present diffusely in the CNS but also form denser regions of extracellular matrix termed perineuronal nets which surround neurons. Hyaluronan is immobilized in hyalectan CS-PG aggregates in these perineural structures, which provide neural protection, synapse, and neural plasticity, and have roles in memory and cognitive learning. Despite the generally inhibitory cues delivered by CS-A and CS-C, some CS-PGs containing highly charged CS disaccharides (CS-D, CS-E) or dermatan sulfate (DS) disaccharides that promote neural outgrowth and functional recovery. CS/DS thus has varied cell regulatory properties and structural ECM supportive roles in the CNS/PNS depending on the glycoform present and its location in tissue niches and specific cellular contexts. Studies on the fruit fly, Drosophila melanogaster and the nematode Caenorhabditis elegans have provided insightful information on neural interconnectivity and the role of the ECM and its PGs in neural development and in tissue morphogenesis in a whole organism environment.

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“…Surface CRT is able to induce an “eat me” signal to phagocytes [ 307 ], increasing their activity along with DC maturation and antigen-presenting function [ 308 ]. The calreticulin effect is antagonized by the interaction of CD47 present on the tumor cell membrane with SIRP-alpha α located on macrophages and DC [ 309 ]), generating a “do not eat me” message in target phagocytes [ 310 ]. Increased expression of HSP90 and HSP70 by ICD inducers [ 247 ].…”

Section: Figurementioning

confidence: 99%

Abscopal Effect and Drug-Induced Xenogenization: A Strategic Alliance in Cancer Treatment?

Franzese

Torino

Giannetti

et al. 2021

IJMS

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The current state of cancer treatment is still far from being satisfactory considering the strong impairment of patients’ quality of life and the high lethality of malignant diseases. Therefore, it is critical for innovative approaches to be tested in the near future. In view of the crucial role that is played by tumor immunity, the present review provides essential information on the immune-mediated effects potentially generated by the interplay between ionizing radiation and cytotoxic antitumor agents when interacting with target malignant cells. Therefore, the radiation-dependent abscopal effect (i.e., a biological effect of ionizing radiation that occurs outside the irradiated field), the influence of cancer chemotherapy on the antigenic pattern of target neoplastic cells, and the immunogenic cell death (ICD) caused by anticancer agents are the main topics of this presentation. It is widely accepted that tumor immunity plays a fundamental role in generating an abscopal effect and that anticancer drugs can profoundly influence not only the host immune responses, but also the immunogenic pattern of malignant cells. Remarkably, several anticancer drugs impact both the abscopal effect and ICD. In addition, certain classes of anticancer agents are able to amplify already expressed tumor-associated antigens (TAA). More importantly, other drugs, especially triazenes, induce the appearance of new tumor neoantigens (TNA), a phenomenon that we termed drug-induced xenogenization (DIX). The adoption of the abscopal effect is proposed as a potential therapeutic modality when properly applied concomitantly with drug-induced increase in tumor cell immunogenicity and ICD. Although little to no preclinical or clinical studies are presently available on this subject, we discuss this issue in terms of potential mechanisms and therapeutic benefits. Upcoming investigations are aimed at evaluating how chemical anticancer drugs, radiation, and immunotherapies are interacting and cooperate in evoking the abscopal effect, tumor xenogenization and ICD, paving the way for new and possibly successful approaches in cancer therapy.

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The role of CD47-SIRPα immune checkpoint in tumor immune evasion and innate immunotherapy

Cited by 49 publications

References 170 publications

Targeting CD47 for cancer immunotherapy

Targeting CD47 for cancer immunotherapy

Neural Tissue Homeostasis and Repair Is Regulated via CS and DS Proteoglycan Motifs

Abscopal Effect and Drug-Induced Xenogenization: A Strategic Alliance in Cancer Treatment?

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