High-dose ascorbic acid synergizes with anti-PD1 in a lymphoma mouse model

Area of Science:

• Immunology
• Epigenetics
• Oncology

Background:

• Immune checkpoint inhibitors (ICIs) like anti-PD1 are crucial cancer therapies.
• Identifying agents to potentiate ICI efficacy is a major research focus.

Purpose of the Study:

• To investigate the potential of ascorbic acid (AA) to enhance anti-PD1 therapy in lymphoma.
• To elucidate the underlying mechanisms of AA's effect on the tumor immune microenvironment and epigenome.

Main Methods:

• In vitro lymphoma cell culture and co-culture systems.
• Syngeneic lymphoma mouse models treated with AA and anti-PD1 therapy.
• Genomewide demethylation analysis, 5-hydroxymethylcytosine (5hmC) level assessment.
• Intratumoral immune cell infiltration and cytokine production analysis.

Main Results:

• Ascorbic acid (AA) treatment induced genomewide demethylation and increased endogenous retroviral element expression in lymphoma cells.
• AA increased CD8+ T cell 5hmC levels and cytotoxic activity, synergizing with anti-PD1 to inhibit tumor growth in vivo.
• Combination therapy significantly enhanced intratumoral CD8+ T cell and macrophage infiltration, granzyme B, and IL-12 production.

Conclusions:

• Ascorbic acid potentiates anti-PD1 checkpoint inhibition through synergistic epigenetic and immunomodulatory mechanisms.
• The study supports clinical trials combining high-dose AA with anti-PD1 for aggressive B cell lymphoma and other cancers.