Novel Immunomodulatory Pathways in the Immunoglobulin Superfamily

Rennert, Paul D.

doi:10.1007/978-3-319-29827-6_2

Cited by 1 publication

(1 citation statement)

References 66 publications

(70 reference statements)

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“…Further, the increase of Tregs in breast tumors correlates with an invasive phenotype and a poor prognosis, and aggressive TNBC is considerably associated with high expression of Tregs [ 71 ]. Notably, small molecules inhibitors of PDGFRβ have been reported to augment tumor immunity by depletion of FoxP3-expressing Tregs and increase in CD8 + T cells in humans and advanced tumor-bearing mice [ 72 – 74 ].…”

Section: Discussionmentioning

confidence: 99%

Aptamer targeted therapy potentiates immune checkpoint blockade in triple-negative breast cancer

Camorani

Passariello

Agnello

et al. 2020

J Exp Clin Cancer Res

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Background: Triple-negative breast cancer (TNBC) is a uniquely aggressive cancer with high rates of relapse due to resistance to chemotherapy. TNBC expresses higher levels of programmed cell death-ligand 1 (PD-L1) compared to other breast cancers, providing the rationale for the recently approved immunotherapy with anti-PD-L1 monoclonal antibodies (mAbs). A huge effort is dedicated to identify actionable biomarkers allowing for combination therapies with immune-checkpoint blockade. Platelet-derived growth factor receptor β (PDGFRβ) is highly expressed in invasive TNBC, both on tumor cells and tumor microenvironment. We recently proved that tumor growth and lung metastases are impaired in mouse models of human TNBC by a high efficacious PDGFRβ aptamer. Hence, we aimed at investigating the effectiveness of a novel combination treatment with the PDGFRβ aptamer and anti-PD-L1 mAbs in TNBC. Methods: The targeting ability of the anti-human PDGFRβ aptamer toward the murine receptor was verified by streptavidin-biotin assays and confocal microscopy, and its inhibitory function by transwell migration assays. The anti-proliferative effects of the PDGFRβ aptamer/anti-PD-L1 mAbs combination was assessed in human MDA-MB-231 and murine 4 T1 TNBC cells, both grown as monolayer or co-cultured with lymphocytes. Tumor cell lysis and cytokines secretion by lymphocytes were analyzed by LDH quantification and ELISA, respectively. Orthotopic 4 T1 xenografts in syngeneic mice were used for dissecting the effect of aptamer/mAb combination on tumor growth, metastasis and lymphocytes infiltration. Ex vivo analyses through immunohistochemistry, RT-qPCR and immunoblotting were performed.

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Section: Discussionmentioning

confidence: 99%