Establishment and Characterization of Humanized Mouse NPC-PDX Model for Testing Immunotherapy

Area of Science:

• Oncology
• Immunology
• Preclinical Models

Background:

• Immune checkpoint blockade (ICB) shows promise for nasopharyngeal carcinoma (NPC) treatment.
• Limited preclinical models hinder the evaluation of novel ICB and combination therapies for NPC.

Purpose of the Study:

• To establish and characterize a humanized mouse NPC-patient-derived xenograft (NPC-PDX) model.
• To evaluate the efficacy of combination immunotherapy (nivolumab and ipilimumab) in this novel NPC model.

Main Methods:

• Engrafted NPC biopsies into NSG mice to create humanized NPC-PDX models.
• Detected Epstein-Barr virus (EBV) using EBER ISH and IHC.
• Assessed T cell infiltration, inhibitory receptor expression (PD-1, CTLA-4), and cytokine profiles (IFN-γ, IL-6) before and after ICB treatment.

Main Results:

• The humanized NPC-PDX model did not respond to ICB treatment in terms of tumor burden, mirroring clinical data.
• ICB treatment elicited an immunomodulatory response, with increased plasma proinflammatory cytokines (IFN-γ, IL-6).
• Tumor-infiltrating T cells showed signs of re-activation, but other factors in the tumor microenvironment may counteract ICB efficacy.

Conclusions:

• A novel humanized mouse NPC-PDX model was successfully established and characterized.
• This model serves as a robust platform for testing immunotherapy efficacy in NPC.
• The model may help predict clinical outcomes for NPC patients undergoing immunotherapy.