Review of immune checkpoint blockade and PD-L1 testing in breast cancer

Baltan, Adelina; Costache, Simona; Shaaban, Abeer M; D'Arrigo, Corrado

doi:10.1016/j.mpdhp.2023.12.001

Diagnostic Histopathology

2024

DOI: 10.1016/j.mpdhp.2023.12.001

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Review of immune checkpoint blockade and PD-L1 testing in breast cancer

Adelina Baltan,

Simona Costache,

Abeer M Shaaban

et al.

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2024

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References 42 publications

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Tumor microenvironment immunomodulation by nanoformulated TLR 7/8 agonist and PI3k delta inhibitor enhances therapeutic benefits of radiotherapy

Yazdimamaghani,

Kolupaev,

Lim

et al. 2024

Preprint

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Infiltration of immunosuppressive cells into the breast tumor microenvironments (TME) is associated with suppressed effector T cell (Teff) responses, accelerated tumor growth, and poor clinical outcomes. Previous studies from our group and others identified infiltration of immunosuppressive myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs) as critical contributors to immune dysfunction in the orthotopic triple-negative breast cancer (TNBC) tumor model limiting adoptive cellular therapy. However, approaches to target these cells specifically in the TME are currently lacking. To overcome this barrier, TNBC polymeric micelles nanoparticles (PMNPs) were used for co-delivery of small molecule drugs activating Toll-like receptors 7 and 8 (TLR7/8) and inhibiting PI3K delta. The immunomodulation of the TME by TLR7/8 agonist and PI3K inhibitor altered macrophage polarization, reduced MDSC accumulation and selectively decreased tissue-resident Tregs in the TME, while enhancing the adaptive immune response. PMNPs significantly enhanced the anti-tumor activity of local radiation therapy (RT) in mice bearing orthotopic TNBC tumors compared to RT alone. Taken together, these data demonstrate that RT combined with a nanoformulated immunostimulant-restructured TME has promising potential for future clinical trials and translation for improved outcomes in TNBC patients.

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Tumor microenvironment immunomodulation by nanoformulated TLR 7/8 agonist and PI3k delta inhibitor enhances therapeutic benefits of radiotherapy

Yazdimamaghani,

Kolupaev,

Lim

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

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Review of immune checkpoint blockade and PD-L1 testing in breast cancer

Cited by 1 publication

References 42 publications

Tumor microenvironment immunomodulation by nanoformulated TLR 7/8 agonist and PI3k delta inhibitor enhances therapeutic benefits of radiotherapy

Tumor microenvironment immunomodulation by nanoformulated TLR 7/8 agonist and PI3k delta inhibitor enhances therapeutic benefits of radiotherapy

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