Quantitative response assessment of combined immunotherapy in a murine melanoma model using multiparametric MRI

Area of Science:

• Oncology
• Radiology
• Immunology

Background:

• Assessing immunotherapy response in melanoma is crucial for treatment optimization.
• Multiparametric magnetic resonance imaging (mpMRI) offers potential for non-invasive monitoring.
• Ex vivo immunohistochemistry provides validation for imaging biomarkers.

Purpose of the Study:

• To evaluate the efficacy of mpMRI in assessing early immunotherapy response in a murine melanoma model.
• To correlate mpMRI-derived features with ex vivo immunohistochemical markers of treatment efficacy.

Main Methods:

• A murine melanoma model (B16-F10) was established in C57BL/6 mice.
• Immunotherapy involved anti-PD-L1 and anti-CTLA-4 antibodies; controls received placebo.
• mpMRI (including ADC and DCE metrics) and ex vivo immunohistochemistry (CD8+ TILs, Ki-67, TUNEL, CD31+) were performed.

Main Results:

• No significant difference in tumor volume was observed between immunotherapy and control groups post-treatment.
• Immunotherapy led to significantly lower apparent diffusion coefficient (ADC) values.
• Immunohistochemistry confirmed increased CD8+ T-cell infiltration, apoptosis (TUNEL), and decreased proliferation (Ki-67) and microvascular density (CD31+) in the immunotherapy group.

Conclusions:

• Lower tumor ADC values correlate with increased CD8+ T-cell infiltration, indicating early immunological response to immunotherapy.
• Diffusion-weighted MRI shows promise for early assessment of immunotherapy response in melanoma, reflecting changes in tumor microenvironment and immune infiltration.
• Ex vivo validation confirmed the antitumoral efficacy of combined anti-PD-L1 and anti-CTLA-4 immunotherapy.