Andrographolide potentiates PD-1 blockade immunotherapy by inhibiting COX2-mediated PGE2 release

Area of Science:

• Immunology
• Oncology
• Pharmacology

Background:

• Cancer immunotherapy, particularly immune checkpoint blockade, faces limitations like low response rates and side effects.
• Andrographolide, a natural compound, possesses anti-inflammatory properties, but its anti-tumor immunity effects are not well understood.

Purpose of the Study:

• To investigate the efficacy of andrographolide in combination with anti-PD-1 antibody therapy for colorectal cancer.
• To elucidate the underlying mechanisms of this combined therapeutic approach.

Main Methods:

• Utilized a murine xenograft model of CT26 colon cancer.
• Assessed T-cell function (CD4+, CD8+), cytokine secretion (IFN-γ), and cytotoxic molecule expression (FasL, perforin, Granzyme B).
• Investigated the role of cyclooxygenase-2 (COX2) activity and prostaglandin E2 (PGE2) release in vitro and in vivo.

Main Results:

• The combination of andrographolide and anti-PD-1 antibody demonstrated superior therapeutic benefit compared to monotherapy.
• Co-treatment enhanced CD4+ and CD8+ T-cell infiltration and function, leading to reduced tumor load.
• Andrographolide inhibited COX2 activity and PGE2 release, augmenting the anti-tumor effects of anti-PD-1 therapy.
• Elevated COX2 levels in human colon cancer samples correlated with tumor-promoting factors.

Conclusions:

• Andrographolide potentiates anti-PD-1 antibody therapy against colorectal cancer.
• The combination strategy enhances T-cell mediated anti-tumor immunity, partly through COX2/PGE2 pathway inhibition.
• This study presents a promising combination strategy for colorectal cancer immunotherapy.