Local and systemic modulation of the PD-L1 pathway is a novel mechanism of Enzalutamide resistance in castration-resistant prostate cancer

Bishop, Jennifer; Sio, Alexander; Angeles, Arkhjamil; Roberts, Morgan E.; Azad, Arun; N., Kim; Zoubeidi, Amina

doi:10.1186/2051-1426-2-s3-p94

Cited by 1 publication

(2 citation statements)

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“…ADT can also enhance T‐cell infiltration in tumors but can be offset by increased Treg differentiation and accumulation 130–132 . Early reports have also shown that increased PD‐L1 expression could be associated with enzalutamide resistance 20,133 . It has recently been shown that AR can limit CD8 T‐cell responses to PD‐1/PD‐L1 blockade by downregulating IFN‐γ, TNF‐α, and granzyme B and driving cells into a terminally exhausted state 134,135 .…”

Section: Immunosuppressive Niches Of the Tme Of Crpcmentioning

confidence: 99%

“…[130][131][132] Early reports have also shown that increased PD-L1 expression could be associated with enzalutamide resistance. 20,133 It has recently been shown that AR can limit CD8 T-cell responses to PD-1/PD-L1 blockade by downregulating IFN-c, TNF-a, and granzyme B and driving cells into a terminally exhausted state. 134,135 The authors showed that anti-PD-1 blockade with ADT plus enzalutamide could reinvigorate antitumor immunity and improve survival in preclinical PCa models; however, a similar approach failed to yield favorable results in human mCRPC.…”

Section: Immunosuppressive Niches Of the Tme Of Crpcmentioning

confidence: 99%

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Moving toward improved immune checkpoint immunotherapy for advanced prostate cancer

De Velasco,

Kura,

Fujita

et al. 2024

Int J of Urology

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Human prostate cancer is a heterogenous malignancy that responds poorly to immunotherapy targeting immune checkpoints. The immunosuppressive tumor microenvironment that is typical of human prostate cancer has been the main obstacle to these treatments. The effectiveness of these therapies is also hindered by acquired resistance, leading to slow progress in prostate cancer immunotherapy. Results from the highly anticipated late‐stage clinical trials of PD‐1/PD‐L1 immune checkpoint blockade in patients with advanced prostate cancer have highlighted some of the obstacles to immunotherapy. Despite the setbacks, there is much that has been learned about the mechanisms that drive resistance, and new strategies are being developed and tested. Here, we review the status of immune checkpoint blockade and the immunosuppressive tumor microenvironment and discuss factors contributing to innate and adaptive resistance to immune checkpoint blockade within the context of prostate cancer. We then examine current strategies aiming to overcome these challenges as well as prospects.

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Section: Immunosuppressive Niches Of the Tme Of Crpcmentioning

confidence: 99%