Stress-glucocorticoid-TSC22D3 axis compromises therapy-induced antitumor immunity

Area of Science:

• Immunology
• Neuroscience
• Oncology

Background:

• Psychological distress is linked to cancer outcomes, but its impact on therapy efficacy is unclear.
• Stress may interfere with the immune system's ability to combat cancer.
• Understanding stress-related mechanisms is crucial for improving cancer treatment.

Purpose of the Study:

• To investigate how psychological stress affects anticancer therapy responses.
• To identify the molecular pathways through which stress impacts anti-tumor immunity.

Main Methods:

• Mouse models of cancer subjected to social defeat stress.
• Analysis of plasma corticosterone, Tsc22d3 expression, and immune cell activation (dendritic cells, T cells).
• Correlation studies in cancer patients linking cortisol, TSC22D3, and mood.

Main Results:

• Social defeat stress in mice reduced tumor therapy response.
• Stress elevated corticosterone and Tsc22d3, inhibiting type I interferon and T cell responses.
• Elevated cortisol, TSC22D3, and negative mood correlated in cancer patients.
• Glucocorticoids and Tsc22d3 in dendritic cells were sufficient to block tumor control.
• Reversing glucocorticoid signaling or Tsc22d3 in dendritic cells restored therapeutic efficacy.

Conclusions:

• Stress-induced glucocorticoids and Tsc22d3 disrupt anti-tumor immune surveillance.
• Targeting the glucocorticoid pathway or Tsc22d3 in dendritic cells may enhance cancer therapy.
• This highlights a critical link between stress, immunity, and cancer treatment success.