Overcoming immunotherapeutic resistance in PDAC: SIRPα-CD47 blockade

Alausa, Abdullahi; Lawal, Khadijat Ayodeji; Babatunde, Oluwakemi Arinola; Obiwulu, E.N.O; Oladokun, Olajumoke Christianah; Fadahunsi, Olumide Samuel; Celestine, Ugwu Obiora; Moses, Emmanuel Ugbede; Rejoice, Akaniro Ifunanya; Adegbola, Peter Ifeoluwa

doi:10.1016/j.phrs.2022.106264

Cited by 10 publications

(5 citation statements)

References 183 publications

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“…Consequently, targeting the SIRP-a-CD47 axis has emerged as a promising therapeutic strategy in cancer immunotherapy, aiming to block this interaction and thereby enhancing the immune system's ability to eliminate tumour cells. 48,49 Therefore, SIRP-a could be one of the possible targets for de-signing the novel bispecic antibody. To link cancer cells to the macrophage, cyclic EPB will be conjugated to the anti-SIRP-a monoclonal antibody as EGFR is known to be overexpressed in many cancer cells.…”

Section: Resultsmentioning

confidence: 99%

Macrophage-engaging peptidic bispecific antibodies (pBsAbs) for immunotherapy via a facile bioconjugation strategy

Shao,

Tang,

Chu

et al. 2024

Chem. Sci.

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Section: Resultsmentioning

confidence: 99%

Macrophage-engaging peptidic bispecific antibodies (pBsAbs) for immunotherapy via a facile bioconjugation strategy

Shao,

Tang,

Chu

et al. 2024

Chem. Sci.

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“…TGF-β1 secreted from TAMs plays a key factor in inducing PD-L1 expression in PDACs by enhancing the interaction between pyruvate kinase M2 (PKM2) and the signal transducer and activator of transcription 1 (STAT1) [74]. The phagocytosis function of TAMs is significantly compromised by "don't eat me" signaling, such as the axis of signal-regulatory proteins (SIRPα) on TAMs-cluster of differentiation 47 (CD47) on PDAC cells [75,76]. Similarly, PDAC cells (e.g., Panc1 cells) express CD24 to escape macrophage phagocytosis by binding with the inhibitory receptor sialic acid-binding Ig-like lectin 10 (Siglec-10), expressed by TAMs [77].…”

Section: Tumor-associated Macrophages (Tams)mentioning

confidence: 99%

Targeted Therapy for Highly Desmoplastic and Immunosuppressive Tumor Microenvironment of Pancreatic Ductal Adenocarcinoma

Olaoba,

Yang,

Adelusi

et al. 2024

Cancers

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Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy with a very poor prognosis. Despite advancements in treatment strategies, PDAC remains recalcitrant to therapies because patients are often diagnosed at an advanced stage. The advanced stage of PDAC is characterized by metastasis, which typically renders it unresectable by surgery or untreatable by chemotherapy. The tumor microenvironment (TME) of PDAC comprises highly proliferative myofibroblast-like cells and hosts the intense deposition of a extracellular matrix component that forms dense fibrous connective tissue, a process called the desmoplastic reaction. In desmoplastic TMEs, the incessant aberration of signaling pathways contributes to immunosuppression by suppressing antitumor immunity. This feature offers a protective barrier that impedes the targeted delivery of drugs. In addition, the efficacy of immunotherapy is compromised because of the immune cold TME of PDAC. Targeted therapy approaches towards stromal and immunosuppressive TMEs are challenging. In this review, we discuss cellular and non-cellular TME components that contain actionable targets for drug development. We also highlight findings from preclinical studies and provide updates about the efficacies of new investigational drugs in clinical trials.

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“…It thus suggests GM-CSF and/or MDSCs to be potential targets for PDAC therapy. Additionally, K-RAS mutations are also involved in the suppression of innate and adaptive anti-tumor immunity through modulating PDAC expressions of immune checkpoints such as PD-L1 and CD47 ( 32 , 33 ), as well as through autophagy-mediated MHC-I downregulation in PDAC ( 34 , 35 ).…”

Section: Pdac-intrinsic Aspects: the Primary Driver Of Immunosuppress...mentioning

confidence: 99%

An integrated overview of the immunosuppression features in the tumor microenvironment of pancreatic cancer

Guo,

Wang,

Gao

2023

Front. Immunol.

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Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest malignancies. It is characterized by a complex and immunosuppressive tumor microenvironment (TME), which is primarily composed of tumor cells, stromal cells, immune cells, and acellular components. The cross-interactions and -regulations among various cell types in the TME have been recognized to profoundly shape the immunosuppression features that meaningfully affect PDAC biology and treatment outcomes. In this review, we first summarize five cellular composition modules by integrating the cellular (sub)types, phenotypes, and functions in PDAC TME. Then we discuss an integrated overview of the cross-module regulations as a determinant of the immunosuppressive TME in PDAC. We also briefly highlight TME-targeted strategies that potentially improve PDAC therapy.

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Overcoming immunotherapeutic resistance in PDAC: SIRPα-CD47 blockade

Cited by 10 publications

References 183 publications

Macrophage-engaging peptidic bispecific antibodies (pBsAbs) for immunotherapy via a facile bioconjugation strategy

Macrophage-engaging peptidic bispecific antibodies (pBsAbs) for immunotherapy via a facile bioconjugation strategy

Targeted Therapy for Highly Desmoplastic and Immunosuppressive Tumor Microenvironment of Pancreatic Ductal Adenocarcinoma

An integrated overview of the immunosuppression features in the tumor microenvironment of pancreatic cancer

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