CAFs complicate immunotherapy

Ferrarelli, Leslie K.

doi:10.1126/scisignal.aar5583

Cited by 2 publications

(1 citation statement)

References 2 publications

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“…Nonetheless, only a small subset of the patients within a large cohort can respond favorably to these immunotherapies 4,5 . Accumulative findings have corelated this with the immunosuppressive tumor microenvironment (TME) [6][7][8] , to which cancer associated fibroblasts (CAFs) greatly contribute [9][10][11][12] . CAFs are heterogeneous stromal cells and are prominent components of the TME in solid tumors and shape the immune ecosystem of TME toward a tolerant and immunosuppressive milieu via multiple mechanisms, including production of multiple cytokines and chemokines that then mediate the recruitment and functional differentiation of innate and adaptive immune cells 7,13,14 .…”

Section: Introductionmentioning

confidence: 99%

Pancreatic Tumor Eradication via Selective PIN1 Inhibition in Cancer Associated Fibroblasts and T Lymphocytes Engagement

Liu

Wen

et al. 2022

Preprint

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Cancer associated fibroblasts (CAFs) support tumors via multiple mechanisms, including maintaining the immunosuppressive tumor microenvironment and limiting infiltration of immune cells. The prolyl isomerase PIN1, whose overexpression in CAFs has not been fully profiled yet, plays critical roles in tumor initiation and progression. To decipher effects of selective PIN1 inhibition in CAFs on pancreatic cancer, we formulate DNA-barcoded micellular systems (DMS) encapsulating PIN1 inhibitor. DMS functionalized with CAFs-targeting antibodies (antiCAFs-DMS) can selectively inhibit PIN1 in CAFs of the tumor, leading to efficacious but temporal tumor inhibitions. We further integrate DNA aptamers (AptT), which can engage CD8+ T lymphocytes, to antiCAFs-DMS and thus prepare the bispecific antiCAFs-DMS-AptT system. AntiCAFs-DMS-AptT shows its potent capacity to eradicate pre-established subcutaneous and orthotopic pancreatic cancer on mice.

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Section: Introductionmentioning

confidence: 99%

Pancreatic Tumor Eradication via Selective PIN1 Inhibition in Cancer Associated Fibroblasts and T Lymphocytes Engagement

Liu

Wen

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

Pancreatic tumor eradication via selective Pin1 inhibition in cancer-associated fibroblasts and T lymphocytes engagement

Liu

Wang

et al. 2022

Nat Commun

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Cancer associated fibroblasts (CAFs) support tumors via multiple mechanisms, including maintaining the immunosuppressive tumor microenvironment and limiting infiltration of immune cells. The prolyl isomerase Pin1, whose overexpression in CAFs has not been fully profiled yet, plays critical roles in tumor initiation and progression. To decipher effects of selective Pin1 inhibition in CAFs on pancreatic cancer, here we formulate a DNA-barcoded micellular system (DMS) encapsulating the Pin1 inhibitor AG17724. DMS functionalized with CAF-targeting anti-FAP-α antibodies (antiCAFs-DMS) can selectively inhibit Pin1 in CAFs, leading to efficacious but transient tumor growth inhibition. We further integrate DNA aptamers (AptT), which can engage CD8+ T lymphocytes, to obtain a bispecific antiCAFs-DMS-AptT system. AntiCAFs-DMS-AptT inhibits tumor growth in subcutaneous and orthotopic pancreatic cancer models.

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CAFs complicate immunotherapy

Abstract: Anti-CSF1R immunotherapy effectively inhibits one suppressive immune cell type but unleashes another through cancer-associated fibroblasts.

Cited by 2 publications

References 2 publications

Pancreatic Tumor Eradication via Selective PIN1 Inhibition in Cancer Associated Fibroblasts and T Lymphocytes Engagement

Pancreatic Tumor Eradication via Selective PIN1 Inhibition in Cancer Associated Fibroblasts and T Lymphocytes Engagement

Pancreatic tumor eradication via selective Pin1 inhibition in cancer-associated fibroblasts and T lymphocytes engagement

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