Blocking “don't eat me” signal of CD47-SIRPα in hematological malignancies, an in-depth review

Russ, Atlantis Dawn; Hua, Anh; Montfort, W.R.; Rahman, Bushra; Riaz, Irbaz Bin; Khalid, Muhammad Umar; Carew, Jennifer S.; Nawrocki, Steffan T.; Persky, Daniel O.; Anwer, Faiz

doi:10.1016/j.blre.2018.04.005

Cited by 146 publications

(117 citation statements)

References 52 publications

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“…Antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) are the major mechanisms underlying R therapeutic effect (26,27). Resistance to ADCC may derive from intrinsic features of immune cells of individual patient, such as FcGRIIIA polymorphism and CD47 expression (28,29); while resistance to CDC is mediated by a low expression level of CD20 and/or high expression levels of membrane-bound complement regulatory proteins (mCRPs), including CD46, CD55 and especially CD59 (27,30). Although few studies have experimentally demonstrated the presence of TPCs in NHL, they are still proposed to exist (31,32).…”

Section: Resistance Of Stem-like Resistant Dlbcl Cells Was Regulated mentioning

confidence: 99%

PI3K/AKT inhibition in tumor propagating cells of DLBCL reverses R-CHOP resistance by destabilizing SOX2

Chen

Zhang

et al. 2019

Preprint

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Drug resistance is a major obstacle for the success of conventional anticancer therapy, and the development of drug resistance is at least partly attributed to tumor propagating cells (TPCs). Up to one-third of diffuse large B cell lymphoma (DLBCL) patients eventually develop resistance to R-CHOP regimen. We found that the TPC proportion was remarkably increased in resistant germinal center B cell-like (GCB) and activated B cell-like (ABC) DLBCL subtypes. Elevated SOX2 was the determinant for resistance development, and SOX2 was phosphorylated by activated PI3K/AKT1 signaling, thus preventing ubiquitin-mediated SOX2 degradation. Furthermore, multiple factors, including BCR, integrins, chemokines and FGFR1/2 signaling, regulated PI3K/AKT1 activation. CDK6 in the GCB subtype and FGFR1/2 in the ABC subtype were SOX2 targets in the PI3K/AKT1 pathway. Chemical inhibition of PI3K/AKT1 in both subtypes, CDK6 in the GCB subtype, and FGFR1/2 in the ABC subtype significantly enhanced the susceptibility of resistant cells to CHO treatment. More importantly, PI3K and FGFR1/2 inhibitors but not a CDK6 inhibitor effectively suppressed the tumor growth of R-CHO-resistant DLBCL cells, most likely by converting TPCs to chemo-sensitive differentiated cells. Therefore, this pro-differentiation therapy against TPCs warrants further study in clinical trials for the treatment of resistant DLBCL.

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Section: Resistance Of Stem-like Resistant Dlbcl Cells Was Regulated mentioning

confidence: 99%

PI3K/AKT inhibition in tumor propagating cells of DLBCL reverses R-CHOP resistance by destabilizing SOX2

Chen

Zhang

et al. 2019

Preprint

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“…TAM are important components of the innate immune response and can be activated in response to microenvironment. These responses can range between anti-tumorigenic (pro-inflammatory and phagocytic towards tumor cells) or pro-tumorigenic (promoting tumor cell survival, metastasis, angiogenesis, as well as suppression of surrounding immune cells) (25). Immunosuppressive macrophage (M2) infiltration has been associated with poor clinical outcomes in several cancer types (3, 26-28).…”

Section: Immune System In T Cell Neoplasms – Rationale For Immunotherapymentioning

confidence: 99%

Novel Immunotherapies for T Cell Lymphoma and Leukemia

Ghione

Moskowitz

Paola

et al. 2018

Curr Hematol Malig Rep

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Purpose of review: novel immunotherapies such as checkpoint inhibitors, bispecific and chimeric antigen receptor T cells are leading to promising responses when treating solid tumors and hematological malignancies. T cell neoplasms include leukemia and lymphomas that are derived from T cells. These are rare diseases with generally poor clinical outcomes. This review describes the rational and preliminary results of these approaches for people with T cell lymphoma and leukemia. Recent findings: for T cell neoplasms, despite significant research effort, only few agents, such as monoclonal antibodies and allogeneic stem cell transplantation, showed some clinical activity. One of the major hurdles to targeting T cell neoplasms is that activation or elimination of T cells, either normal or neoplastic, can cause significant toxicity. A need to develop novel safe and effective immunotherapies for T cell neoplasms exists. Summary: In this review, we will discuss the rationale for immunotherapy of T cell leukemia and lymphoma and present the most recent therapeutic approaches.

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“…CD47 surface glycoprotein (integrin-associated protein) ligates signal-regulatory protein alpha on macrophages, initiating selfrecognition and inhibiting phagocytosis. 5,6 Malignant cells show high expression of CD47 and are resistant to phagocytosis. Anti-CD47 aims to prompt the destruction of malignant cells by blocking CD47 positive cells allowing for phagocytosis.…”

mentioning

confidence: 99%

Two case reports involving therapeutic monoclonal anti‐CD47 (Hu5F9‐G4), it's effect on compatibility testing and subsequent selection of components for transfusion

Reyland

Dwight

Bullock

et al. 2020

Transfusion Medicine

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Blocking “don't eat me” signal of CD47-SIRPα in hematological malignancies, an in-depth review

Cited by 146 publications

References 52 publications

PI3K/AKT inhibition in tumor propagating cells of DLBCL reverses R-CHOP resistance by destabilizing SOX2

PI3K/AKT inhibition in tumor propagating cells of DLBCL reverses R-CHOP resistance by destabilizing SOX2

Novel Immunotherapies for T Cell Lymphoma and Leukemia

Two case reports involving therapeutic monoclonal anti‐CD47 (Hu5F9‐G4), it's effect on compatibility testing and subsequent selection of components for transfusion

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