Dataset Information

The Sympathetic Nervous System Modulates Cancer Vaccine Activity through Monocyte-Derived Cells.

ABSTRACT: The sympathetic nervous system (SNS) is an important regulator of immune cell function during homeostasis and states of inflammation. Recently, the SNS has been found to bolster tumor growth and impair the development of antitumor immunity. However, it is unclear whether the SNS can modulate APC function. Here, we investigated the effects of SNS signaling in murine monocyte-derived macrophages (moMФ) and dendritic cells (DCs) and further combined the nonspecific β-blocker propranolol with a peptide cancer vaccine for the treatment of melanoma in mice. We report that norepinephrine treatment dramatically altered moMФ cytokine production, whereas DCs were unresponsive to norepinephrine and critically lack β₂-adrenergic receptor expression. In addition, we show that propranolol plus cancer vaccine enhanced peripheral DC maturation, increased the intratumor proportion of effector CD8⁺ T cells, and decreased the presence of intratumor PD-L1⁺ myeloid-derived suppressor cells. Furthermore, this combination dramatically reduced tumor growth compared with vaccination alone. Taken together, these results offer insights into the cell-specific manner by which the SNS regulates the APC immune compartment and provide strong support for the use of propranolol in combination with cancer vaccines to improve patient response rates and survival.

SUBMITTER: Hinkle L

PROVIDER: S-EPMC9583274 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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The Sympathetic Nervous System Modulates Cancer Vaccine Activity through Monocyte-Derived Cells.

Hinkle Louis L Liu Yongbin Y Meng Chaoyang C Chen Zhe Z Mai Junhua J Zhang Licheng L Xu Yitian Y Pan Ping-Ying PY Chen Shu-Hsia SH Shen Haifa H

Journal of immunology (Baltimore, Md. : 1950) 20211112 12

The sympathetic nervous system (SNS) is an important regulator of immune cell function during homeostasis and states of inflammation. Recently, the SNS has been found to bolster tumor growth and impair the development of antitumor immunity. However, it is unclear whether the SNS can modulate APC function. Here, we investigated the effects of SNS signaling in murine monocyte-derived macrophages (moMФ) and dendritic cells (DCs) and further combined the nonspecific β-blocker propranolol with a pept ...[more]

PMID: 34772699

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Project description:BACKGROUND AND PURPOSE:Poststroke hemiparesis increases the perceived challenge of walking. Perceived challenge is commonly measured by self-report, which is susceptible to measurement bias. A promising approach to objectively assess perceived challenge is measuring sympathetic nervous system (SNS) activity with skin conductance to detect the physiological stress response. We investigated the feasibility of using skin conductance measurements to detect task-related differences in the challenge posed by complex walking tasks in adults poststroke. METHODS:Adults poststroke (n = 31) and healthy young adults (n = 8) performed walking tasks including typical walking, walking in dim lighting, walking over obstacles, and dual-task walking. Measures of skin conductance and spatiotemporal gait parameters were recorded. Continuous decomposition analysis was conducted to assess changes in skin conductance level (?SCL) and skin conductance response (?SCR). A subset of participants poststroke also underwent a 12-week rehabilitation intervention. RESULTS:SNS activity measured by skin conductance (both ?SCL and ?SCR) was significantly greater for the obstacles task and dual-task walking than for typical walking in the stroke group. Participants also exhibited "cautious" gait behaviors of slower speed, shorter step length, and wider step width during the challenging tasks. Following the rehabilitation intervention, SNS activity decreased significantly for the obstacles task and dual-task walking. DISCUSSION AND CONCLUSIONS:SNS activity measured by skin conductance is a feasible approach for quantifying task-related differences in the perceived challenge of walking tasks in people poststroke. Furthermore, reduced SNS activity during walking following a rehabilitation intervention suggests a beneficial reduction in the physiological stress response evoked by complex walking tasks.Video Abstract available for more insights from the authors (See Video, Supplemental Digital Content 1, http://links.lww.com/JNPT/A234).

Dataset Information

The Sympathetic Nervous System Modulates Cancer Vaccine Activity through Monocyte-Derived Cells.

Publications

The Sympathetic Nervous System Modulates Cancer Vaccine Activity through Monocyte-Derived Cells.

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