Cancer cells under immune attack acquire CD47-mediated adaptive immune resistance independent of the myeloid CD47-SIRPα axis

Hendriks, Mark A J M; Britsch, Isabel; Ke, Xiurong; Wijngarden, Anne P. van; Samplonius, Douwe F.; Ploeg, Emily M.; Helfrich, Wijnand

doi:10.1080/2162402x.2021.2005344

Cited by 5 publications

(2 citation statements)

References 22 publications

(26 reference statements)

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“…Combinatorial treatment with TEDbodies and agonistic OX40 antibody had beneficial outcomes and warrants further investigations [39]. Recently, we discovered that cancer cells dynamically enhance CD47 cell surface expression, which coincided with acquiring resistance to pro-apoptotic effector T cell mechanisms [104]. Therefore, treatments combining anti-CMV CD8 pos T cell recruitment and CD47-blocking antibodies should be considered to improve their efficacy.…”

Section: Discussionmentioning

confidence: 99%

Applications of Anti-Cytomegalovirus T Cells for Cancer (Immuno)Therapy

Britsch,

van Wijngaarden,

Helfrich

2023

Cancers

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Infection with cytomegalovirus (CMV) is highly prevalent in the general population and largely controlled by CD8pos T cells. Intriguingly, anti-CMV T cells accumulate over time to extraordinarily high numbers, are frequently present as tumor-resident ‘bystander’ T cells, and remain functional in cancer patients. Consequently, various strategies for redirecting anti-CMV CD8pos T cells to eliminate cancer cells are currently being developed. Here, we provide an overview of these strategies including immunogenic CMV peptide-loading onto endogenous HLA complexes on cancer cells and the use of tumor-directed fusion proteins containing a preassembled CMV peptide/HLA-I complex. Additionally, we discuss conveying the advantageous characteristics of anti-CMV T cells in adoptive cell therapy. Utilization of anti-CMV CD8pos T cells to generate CAR T cells promotes their in vivo persistence and expansion due to appropriate co-stimulation through the endogenous (CMV-)TCR signaling complex. Designing TCR-engineered T cells is more challenging, as the artificial and endogenous TCR compete for expression. Moreover, the use of expanded/reactivated anti-CMV T cells to target CMV peptide-expressing glioblastomas is discussed. This review highlights the most important findings and compares the benefits, disadvantages, and challenges of each strategy. Finally, we discuss how anti-CMV T cell therapies can be further improved to enhance treatment efficacy.

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Section: Discussionmentioning

confidence: 99%

Applications of Anti-Cytomegalovirus T Cells for Cancer (Immuno)Therapy

Britsch,

van Wijngaarden,

Helfrich

2023

Cancers

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“…By blocking the connection between CD47 and SIRPa, anti-CD47 antibodies may improve macrophages' ability to fight tumors (246,247). Blocking the CD47/SIRPa pathway had promising results in treatment of several solid tumors and hematological cancers such as glioblastoma, lymphoma, and breast cancer and may compel TAMs to phagocytose tumor cells (246,(248)(249)(250)(251)(252)(253)(254)(255). Other strategies for harnessing or restoring antitumor properties of macrophages are discussed below.…”

Section: Cd47/sirpa Checkpointmentioning

confidence: 99%

The cross-talk between macrophages and tumor cells as a target for cancer treatment

Aizaz,

Khan,

Khan

et al. 2023

Front. Oncol.

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Macrophages represent an important component of the innate immune system. Under physiological conditions, macrophages, which are essential phagocytes, maintain a proinflammatory response and repair damaged tissue. However, these processes are often impaired upon tumorigenesis, in which tumor-associated macrophages (TAMs) protect and support the growth, proliferation, and invasion of tumor cells and promote suppression of antitumor immunity. TAM abundance is closely associated with poor outcome of cancer, with impediment of chemotherapy effectiveness and ultimately a dismal therapy response and inferior overall survival. Thus, cross-talk between cancer cells and TAMs is an important target for immune checkpoint therapies and metabolic interventions, spurring interest in it as a therapeutic vulnerability for both hematological cancers and solid tumors. Furthermore, targeting of this cross-talk has emerged as a promising strategy for cancer treatment with the antibody against CD47 protein, a critical macrophage checkpoint recognized as the “don’t eat me” signal, as well as other metabolism-focused strategies. Therapies targeting CD47 constitute an important milestone in the advancement of anticancer research and have had promising effects on not only phagocytosis activation but also innate and adaptive immune system activation, effectively counteracting tumor cells’ evasion of therapy as shown in the context of myeloid cancers. Targeting of CD47 signaling is only one of several possibilities to reverse the immunosuppressive and tumor-protective tumor environment with the aim of enhancing the antitumor response. Several preclinical studies identified signaling pathways that regulate the recruitment, polarization, or metabolism of TAMs. In this review, we summarize the current understanding of the role of macrophages in cancer progression and the mechanisms by which they communicate with tumor cells. Additionally, we dissect various therapeutic strategies developed to target macrophage–tumor cell cross-talk, including modulation of macrophage polarization, blockade of signaling pathways, and disruption of physical interactions between leukemia cells and macrophages. Finally, we highlight the challenges associated with tumor hypoxia and acidosis as barriers to effective cancer therapy and discuss opportunities for future research in this field.

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CD47-mediated immune evasion in early-stage lung cancer progression

Chuang,

Zhen,

et al. 2024

Biochemical and Biophysical Research Communications

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Cancer cells under immune attack acquire CD47-mediated adaptive immune resistance independent of the myeloid CD47-SIRPα axis

Cited by 5 publications

References 22 publications

Applications of Anti-Cytomegalovirus T Cells for Cancer (Immuno)Therapy

Applications of Anti-Cytomegalovirus T Cells for Cancer (Immuno)Therapy

The cross-talk between macrophages and tumor cells as a target for cancer treatment

CD47-mediated immune evasion in early-stage lung cancer progression

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