Mannosylated-serum albumin nanoparticle imaging to monitor tumor-associated macrophages under anti-PD1 treatment

Background Immune checkpoint inhibitors such as anti-programmed cell death protein 1 (PD1) block tumor growth by reinvigorating the immune system; however, determining their efcacy only by the changes in tumor size may prove inaccurate. As the immune cells including macrophages in the tumor microenvironment (TME) are associ‑ ated with the response to anti-PD1 therapy, tumor-associated macrophages (TAMs) imaging using nanoparticles can noninvasively provide the immune enrichment status of TME. Herein, the mannosylated-serum albumin (MSA) nano‑ particle was labeled with radioactive isotope 68Ga to target the mannose receptors on macrophages for noninvasive monitoring of the TME according to anti-PD1 therapy. Results B16F10-Luc and MC38-Luc tumor-bearing mice were treated with anti-PD1, and the response to anti-PD1 was determined by the tumor volume. According to the fow cytometry, the responders to anti-PD1 showed an increased proportion of TAMs, as well as lymphocytes, and the most enriched immune cell population in the TME was also TAMs. For noninvasive imaging of TAMs as a surrogate of immune cell augmentation in the TME via anti-PD1, we acquired [ 68Ga] Ga-MSA positron emission tomography. According to the imaging study, an increased number of TAMs in responders at the early phase of anti-PD1 treatment was observed in both B16F10-Luc and MC38-Luc tumorbearing mice models. Conclusion As representative immune cells in the TME, non-invasive imaging of TAMs using MSA nanoparticles can refect the immune cell enrichment status in the TME closely associated with the response to anti-PD1. As non-inva‑ sive imaging using MSA nanoparticles, this approach shows a potential to monitor and evaluate anti-tumor response to immune checkpoint inhibitors.This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Education (NRF-2020R1A6A3A13069409), the Korean government the Ministry of Science, ICT and Future Planning (2020R1A2C2010202, 2020R1A4A2002903, 2020M3A9B6038086, 2021M2E7A2079570, 2021R1A2C3009427, 2022M3E5F2018261), and the Ministry of Health and Welfare (HI19C0339, HN22C0644). This study also was carried out by the research fund supported by the fund project of Park Yang Sook - Chung Yung Ho in Seoul National University

Low serum cartonectin/CTRP3 concentrations in newly diagnosed type 2 diabetes mellitus: in vivo regulation of cartonectin by glucose.

OBJECTIVES Cartonectin is a novel adipokine of the C1q complement/TNF-related protein (CTRP) superfamily, with glucose lowering effects, anti-inflammatory and cardio-protective properties. We sought to investigate circulating cartonectin concentrations in subjects with type 2 diabetes mellitus (T2DM) as well as age and BMI matched control subjects. We also examined the effects of a 2 hour 75 g oral glucose tolerance test (OGTT) on serum cartonectin concentrations in T2DM subjects. DESIGN Cross-sectional study [newly diagnosed (first discovery, not on any treatments) T2DM (n = 47) and control (n = 63) subjects]. Serum cartonectin was measured by ELISA. RESULTS Serum cartonectin concentrations were significantly lower in patients with T2DM compared to controls (P0.05). There were no significant correlations in T2DM subjects (n = 47). In control subjects (n = 63), serum cartonectin was significantly negatively correlated with CRP, and significantly positively correlated with insulin, HOMA-IR and leptin. However, when subjected to multiple regression analysis, none of these variables were predictive of serum cartonectin (P>0.05). Finally, serum cartonectin concentrations were significantly lower in T2DM subjects after a 2 hour 75 g OGTT (P<0.01). CONCLUSIONS Cartonectin may serve as a novel biomarker for the prediction and early diagnosis of T2DM patients. Furthermore, cartonectin and/or pharmacological agents that increase circulating cartonectin levels can represent a new therapeutic field in the treatment of T2DM patients. Further research is needed to clarify these points