Reply to Comment on Katsarelias, D., et al. “The Effect of Beta-Adrenergic Blocking Agents in Cutaneous Melanoma—A Nation-Wide Swedish Population-Based Retrospective Register Study.” Cancers 2020, 12, 3228

Katsarelias, Dimitrios; Eriksson, Hanna; Mikiver, Rasmus; Krakowski, I.; Nilsson, Jonas A.; Ny, Lars; Bagge, Roger Olofsson

doi:10.3390/cancers13010092

Cancers

2020

DOI: 10.3390/cancers13010092

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Reply to Comment on Katsarelias, D., et al. “The Effect of Beta-Adrenergic Blocking Agents in Cutaneous Melanoma—A Nation-Wide Swedish Population-Based Retrospective Register Study.” Cancers 2020, 12, 3228

Dimitrios Katsarelias

Hanna Eriksson

Rasmus Mikiver

et al.

Abstract: We thank De Giorgi et al for their interest in our study, and for raising important and relevant questions [...]

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Targeting beta-adrenergic receptor pathways in melanoma: how stress modulates oncogenic immunity

Switzer,

Puzanov,

Gandhi

et al. 2023

Melanoma Research

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The intricate pathways of the sympathetic nervous system hold an inherently protective role in the setting of acute stress. This is achieved through dynamic immunomodulatory and neurobiological networks. However, excessive and chronic exposure to these stress-induced stimuli appears to cause physiologic dysfunction through several mechanisms that may impair psychosocial, neurologic, and immunologic health. Numerous preclinical observations have identified the beta-2 adrenergic receptor (β2-AR) subtype to possess the strongest impact on immune dysfunction in the setting of chronic stressful stimuli. This prolonged expression of β2-ARs appears to suppress immune surveillance and promote tumorigenesis within multiple cancer types. This occurs through several pathways, including (1) decreasing the frequency and function of CD8 + T-cells infiltrating the tumor microenvironment (TME) via inhibition of metabolic reprogramming during T cell activation, and (2) establishing an immunosuppressive profile within the TME including promotion of an exhausted T cell phenotype while simultaneously enhancing local and paracrine metastatic potential. The use of nonselective β-AR antagonists appears to reverse many chronic stress-induced tumorigenic pathways and may also provide an additive therapeutic benefit for various immune checkpoint modulating agents including commonly utilized immune checkpoint inhibitors. Here we review the translational and clinical observations highlighting the foundational hypotheses that chronic stress-induced β-AR signaling promotes a pro-tumoral immunophenotype and that blockade of these pathways may augment the therapeutic response of immune checkpoint inhibition within the scope of melanoma.

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Targeting beta-adrenergic receptor pathways in melanoma: how stress modulates oncogenic immunity

Switzer,

Puzanov,

Gandhi

et al. 2023

Melanoma Research

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show abstract

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Reply to Comment on Katsarelias, D., et al. “The Effect of Beta-Adrenergic Blocking Agents in Cutaneous Melanoma—A Nation-Wide Swedish Population-Based Retrospective Register Study.” Cancers 2020, 12, 3228

Abstract: We thank De Giorgi et al for their interest in our study, and for raising important and relevant questions [...]

Cited by 1 publication

References 3 publications

Targeting beta-adrenergic receptor pathways in melanoma: how stress modulates oncogenic immunity

Targeting beta-adrenergic receptor pathways in melanoma: how stress modulates oncogenic immunity

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