Propranolol reduces IFN-γ driven PD-L1 immunosuppression and improves anti-tumour immunity in ovarian cancer

Falcinelli, Marta; Al-Hity, Gheed; Baron, S.; Mampay, Myrthe; Allen, Marcus; Samuels, Mark E.; Jones, Wendell; Cilibrasi, Chiara; Flaherty, Renée L.; Giamas, Georgios; Thaker, Premal H.; Flint, Melanie S.

doi:10.1016/j.bbi.2023.02.011

Cited by 16 publications

(6 citation statements)

References 55 publications

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“…This assumption is supported by the observation that clenbuterol, a long-acting β-AR agonist, was shown to induce cell proliferation [236] and that β-AR activation caused an increase in LD number and lipid content [170] in breast cancer cell lines. The putative clinical relevance of a pro-tumorigenic effect of β-AR activation is further supported by reports showing that the chronic use of β-AR antagonists decreases the incidence or mortality of many cancer types [237][238][239][240][241][242][243].…”

Section: Modulators Of Camp/pka Pathwaymentioning

confidence: 87%

Challenges in Pharmacological Intervention in Perilipins (PLINs) to Modulate Lipid Droplet Dynamics in Obesity and Cancer

Bombarda-Rocha,

Silva,

Badr-Eddine

et al. 2023

Cancers

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Perilipins (PLINs) are the most abundant proteins in lipid droplets (LD). These LD-associated proteins are responsible for upgrading LD from inert lipid storage structures to fully functional organelles, fundamentally integrated in the lipid metabolism. There are five distinct perilipins (PLIN1–5), each with specific expression patterns and metabolic activation, but all capable of regulating the activity of lipases on LD. This plurality creates a complex orchestrated mechanism that is directly related to the healthy balance between lipogenesis and lipolysis. Given the essential role of PLINs in the modulation of the lipid metabolism, these proteins can become interesting targets for the treatment of lipid-associated diseases. Since reprogrammed lipid metabolism is a recognized cancer hallmark, and obesity is a known risk factor for cancer and other comorbidities, the modulation of PLINs could either improve existing treatments or create new opportunities for the treatment of these diseases. Even though PLINs have not been, so far, directly considered for pharmacological interventions, there are many established drugs that can modulate PLINs activity. Therefore, the aim of this study is to assess the involvement of PLINs in diseases related to lipid metabolism dysregulation and whether PLINs can be viewed as potential therapeutic targets for cancer and obesity.

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Section: Modulators Of Camp/pka Pathwaymentioning

confidence: 87%

Challenges in Pharmacological Intervention in Perilipins (PLINs) to Modulate Lipid Droplet Dynamics in Obesity and Cancer

Bombarda-Rocha,

Silva,

Badr-Eddine

et al. 2023

Cancers

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“…To understand the specific cellular mechanisms of how BBs work in conjunction with immunotherapy, recent research in 2023 indicated that PRO combined with Immunotherapy, such as program death ligand 1 (PD-L1) inhibitors could prevent PD-L1 overexpression in ovarian cancer. This proposes a potentially more targeted response to PD-L1 inhibitors due to possible intrinsic PD-L1 expression in cancer cells ( Falcinelli et al, 2023 ). The implication of this finding suggests that BBs could enhance the effectiveness of immune checkpoint therapy.…”

Section: Enhancing Cancer Immunotherapy With Beta Blockersmentioning

confidence: 99%

Repurposing beta-blockers for combinatory cancer treatment: effects on conventional and immune therapies

Massalee,

Cao

2024

Front. Pharmacol.

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Beta-adrenergic receptor signaling regulates cellular processes associated with facilitating tumor cell proliferation and dampening anti-tumor immune response. These cellular processes may lead to compromised tumor control and cancer progression. Based on this ramification, Beta-blockers (BBs) have emerged as a potential treatment by inhibiting beta-adrenergic receptor signaling. This review aimed to investigate the relationship between the use of BBs and tumor progression and treatment response. Therefore, the authors explored several aspects: the potential synergistic relationship of BBs with chemotherapy and immunotherapy in enhancing the effectiveness of chemotherapeutic and immunotherapeutic treatments and their role in boosting endogenous immunity. Further, this review explores the distinctions between the major types of BBs: Non-selective Beta Blockers (NSBBs) and Selective Beta Blockers (SBBs), and their contributions to combinatory cancer treatment. In this review, we presented a perspective interpretation of research findings and future directions. Overall, this review discusses the potential and challenge that BBs present in improving the effectiveness and outcome of cancer treatment.

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“…For instance, research conducted on breast cancer cells subjected to the β-AR antagonist propranolol has revealed heightened levels of the tumor suppressor protein p53 and augmented cellular demise ( Montoya et al, 2019 ). Propranolol has also exhibited efficacy in alleviating immune suppression facilitated by IFN-γ-induced PD-L1 expression in ovarian cancer ( Falcinelli et al, 2023 ). Additional β1-AR blockers such as Nebivolol, Bisoprolol, and Landiolol have similarly exhibited potential in bolstering antitumor immune responses across various cancer categories, thereby potentially enhancing patient prognoses ( Niu et al, 2021 ; Farhoumand et al, 2023 ; Jin et al, 2023 ; Li F. et al, 2023 ; Shahid et al, 2023 ; Springer et al, 2023 ; Yuan et al, 2023 ).…”

Section: Targeting Chronic Stress For Enhanced Anticancer Therapiesmentioning

confidence: 99%

“…Decreasing the expression of ELK1, C-FOS, NF-κB (Kawahara et al, 2016;Nagata et al, 2020) α1a-AR Silodosin Glioma, OSCC Upregulation of Autophagy (Liu B. et al, 2021;Xing et al, 2023) α1a-AR Doxazosin PCa, AML, Inhibiting the PI3K/Akt/mTOR pathway Sun et al, 2020;Liu D. et al, 2021) α1a-AR Prazosin PCa, BCa, carcinoma, OC, CCRCC Regulation of Bcl-2 (Shimizu et al, 2020;Florent et al, 2020a,b;Zhong et al, 2021) α1a-AR Naproxen Melanoma, NSCLC, BC Boosting Caspase-3/7; ActivityFBXL2-Grp94-EGFR (Niu et al, 2021;Farhoumand et al, 2023; β1-AR Nebivolol Hepatoma, PCa, NSCLC Inhibition of (FBXL10, TRAF6) (Springer et al, 2023;Yuan et al, 2023) β1-AR Bisoprolol NSCLC Inhibiting β1-AR (Jin et al, 2023) β1-AR Landiolol NSCLC Blocking ELK-1, AhR, NF-κB Activities (Shahid et al, 2023) β1-AR Carvedilol Melanoma, CRC, BC, OC, PCa Inhibiting AKT/MAPK; β-ARs and COX-2 Inhibition; CD8 T-cell Priming Suppression; IFN-γ and PD-L1 Reduction; Decrease EMT (Sorski et al, 2016;Shaashua et al, 2017;Haldar et al, 2018Haldar et al, , 2020Daher et al, 2019;Ricon et al, 2019;Hiller et al, 2020;Liao et al, 2020;Liang et al, 2021;Li et al, 2022;Falcinelli et al, 2023) β-ARs Propranolol GC, LUAD, melanoma, hepatoma Suppression of the ERK1/2-JNK-MAPK pathway; β2-ARs/CCL2 axis (Zhang et al, 2019;Zhang B. et al, 2020;Liu C. et al, 2021;Ji et al, 2022) β2-AR ICI118551 BC, NB, melanoma IFN-γ, PD-1/PD-L1; SK2/S1P2 Hemato-differentiation enhancement Calvani et al, 2020;Bruno et al, 2023) β3-AR SR59230A Additionally, α 1-AR blockers have the potential to mitigate adverse effects and enhance the efficacy of CAR-T cell therapy…”

Section: Renal Cancermentioning

confidence: 99%

Investigating the crosstalk between chronic stress and immune cells: implications for enhanced cancer therapy

Lei,

Liao,

Tian

et al. 2023

Front. Neurosci.

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Chronic stress has a substantial influence on the tumor microenvironment (TME), leading to compromised effectiveness of anti-cancer therapies through diverse mechanisms. It disrupts vital functions of immune cells that play a critical role in anti-tumor immunity, such as the inhibition of dendritic cells (DCs) and lymphocytes, while simultaneously enhancing the activity of immune cells that support tumor growth, such as myeloid-derived suppressor cells and tumor-associated macrophages. Furthermore, chronic stress exerts a significant impact on crucial mechanisms within the TME, including angiogenesis, DNA repair, hypoxia, extracellular matrix deposition, and tumor metabolism. These alterations in the TME, induced by stress, result from the activation of the hypothalamic–pituitary–adrenal axis and sympathetic nervous system, in conjunction with epigenetic modifications. In conclusion, chronic stress significantly influences the TME and impedes the efficacy of anti-cancer treatments, underscoring the importance of targeting stress pathways to improve therapeutic results.

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Propranolol reduces IFN-γ driven PD-L1 immunosuppression and improves anti-tumour immunity in ovarian cancer

Cited by 16 publications

References 55 publications

Challenges in Pharmacological Intervention in Perilipins (PLINs) to Modulate Lipid Droplet Dynamics in Obesity and Cancer

Challenges in Pharmacological Intervention in Perilipins (PLINs) to Modulate Lipid Droplet Dynamics in Obesity and Cancer

Repurposing beta-blockers for combinatory cancer treatment: effects on conventional and immune therapies

Investigating the crosstalk between chronic stress and immune cells: implications for enhanced cancer therapy

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