In Vivo Immunoscoring Technique to Monitor Anti-CD47 Immunotherapy Efficacy in Triple-Negative Breast Cancer.

Background

Phagocytosis checkpoints, such as CD47, have emerged as promising targets for cancer immunotherapy and are being investigated in clinical trials. Despite encouraging findings, reliable biomarkers for monitoring immunotherapeutic responses in triple-negative breast cancer (TNBC) remain tracking.

Objective

The objective of this project is to characterize the functional states of tumor-associated macrophages (TAMs) using macrophage-related imaging probes and assess their potential for monitoring responses to anti-CD47 immunotherapy.

Results

Anatomical imaging visualized tumor nodule formation and angiogenesis in tumor-bearing mice. Conventional fluorescence imaging demonstrated the TNBC-targeting ability of monocyte chemoattractant protein-1 (MCP-1) fluorescein isothiocyanate (FITC) and Dextran-Alexa Fluor 680 (AF 680). Intravital imaging elucidated the pharmacokinetics of the imaging probes in TAMs following intravenous injection. These probes preferentially targeted macrophages, as confirmed by the colocalization between F4/80-, CD86-, and CD206-binding cells and imaging probe-targeted cells. Tumor-bearing mice that received intravenous injections of the imaging probes were sacrificed, and the TNBC tissue was cryo-sectioned, stained, and imaged on a confocal microscope, showing a high molecular targeting ability of the imaging probes for macrophages. The M1/M2 macrophage ratio was quantified for monitoring the response to anti-CD47 immunotherapy, which demonstrated that MCP-1 and Dextran are useful tools for M1 and M2 macrophage identification.

Conclusion

The study documents a molecularly targeted construct for TAMs in vivo and verifies proof of the utility of using the M1/M2 ratio as a strategy for monitoring the response to CD47 treatment.