Calorie Restriction Impairs Anti-Tumor Immune Responses in an Immunogenic Preclinical Cancer Model

Area of Science:

• Immunology
• Oncology
• Metabolism

Background:

• Dietary energy intake influences cancer progression and immunity.
• The impact of calorie restriction (CR) on anti-tumor immune responses is not well understood.

Purpose of the Study:

• To investigate the effect of CR on B16 melanoma tumor growth and host immune responses.
• To determine if CR affects the efficacy of cancer immunotherapy, specifically anti-PD-1 antibody treatment.

Main Methods:

• Utilized B16 melanoma cells expressing ovalbumin (B16-OVA) in mice.
• Assessed tumor growth, CD4+ and CD8+ T cell infiltration, and response to anti-PD-1 antibody treatment under CR and control diets.
• Investigated the role of CD8+ T cells by in vivo depletion.

Main Results:

• CR significantly slowed B16-OVA tumor growth without altering CD4+ or CD8+ T cell infiltration.
• CD8+ T cell depletion accelerated tumor growth in control mice but not in CR mice.
• CR abolished the efficacy of anti-PD-1 antibody treatment, associated with altered CD8+ T cell activation and metabolism.

Conclusions:

• Calorie restriction may impair CD8+ T cell-mediated immune surveillance against tumors.
• CR can compromise the effectiveness of anti-PD-1 immunotherapy in preclinical models.
• Energy-restricted conditions in cancer patients might hinder anti-tumor immunity and immunotherapy outcomes.