Pilot: MR Imaging of Tumor Associated Macrophage Changes with Therapy

Principal Investigator: Chapelin, Fanny 18.2 2. PROJECT TITLE: MR imaging of tumor associated macrophage changes with therapy ABSTRACT Background When functioning correctly, the immune system is a strong shield which actively prevents disease and neoplastic development through immunosurveillance. Cancer cells evade the immune system through immunoediting and begin recruiting anti-inflammatory macrophages, referred to as tumor-associated macrophages (TAM). TAM infiltration in tumors is an established biomarker of tumor aggressiveness and tumor resistance to therapy. To assay immune cellular infiltrates in tissue, one generally relies on tissue biopsy, which is invasive and only provides a crude sampling of the diseased sites. Magnetic resonance imaging (MRI)-based cell tracking techniques have proven successful in monitoring immune cell migration to the foci of inflammation in different pathologies, including cancer. Objective We propose to develop non-invasive MRI imaging methods that could serve as prognostic biomarkers of therapy efficacy or tumor recurrence. Specific Aims AIM 1: MR imaging of macrophage recruitment as a predictive biomarker of immunotherapy efficacy. We anticipate that PD-1 immunotherapy will promote TAM conversion from pro-tumor (M2) to anti-tumor (M1) phenotype, and stimulate recruitment of immune cells to the tumor, resulting in significant MR signal change, correlating to tumor growth reduction. AIM 2: MR imaging of macrophage recruitment a s a prognostic tool for tumor recurrence following radiation therapy. Based on the mechanism of macrophage recruitment, we aim to correlate significant MR signal changes to tumor recurrence. Non-invasive MR will enable early detection of tumor recurrence compared to current histopathology and imaging gold standard. Study design We will deliver nanoparticles intravenously to immunocompromised mice bearing subcutaneous human head and neck tumors. This will enable labeling of systemic monocytes, macrophages and TAM, and we will quantify longitudinal MR signal changes following radiation therapy or PD-1 immunotherapy. Cancer Relevance This project will establish a novel and broadly-enabling non-invasive diagnostic tool for detection of cancer therapy efficacy. The ultimate goal is the translation of this straightforward method from bench to bedside, leading to more personalized patient management and improved survival outcomes. This will enable rapid evaluation by clinicians of patients most likely to relapse following radiation therapy and those likely to respond positively to PD-1 immunotherapy. Institutional Research Grant American Cancer Society – February 2021