Introduction: With the spread of immune checkpoint inhibitors (ICIs), it is urgent to pursue novel noninvasive biomarkers of responses to ICIs that allow the “early” determination of clinical benefits. Recently, immune cells in the tumor microenvironment are thought to produce fucosylated haptoglobin as a result from immunohistochemical study (IHC) associating with tumor immunity. Thus, the evaluation of fucosylated haptoglobin in the peripheral blood has the potential to demonstrate noninvasive predictive biomarkers for the clinical efficacy of ICIs. Methods: In this study, a total of 31 advanced renal cell carcinoma (RCC) patients treated with PD-1 antibody (Nivolumab) were enrolled and defined as the patients of responder (CR, PR and long SD, n = 21) and non-responder (Short SD and PD, n = 10) by RECIST criteria. We collected plasma samples before and 1, 3 months after starting treatment and performed ELISA analysis of plasma samples using 10-7G monoclonal antibody that specifically recognizes fucosylated haptoglobin. Results: We first measured total haptoglobin (tHP) before anti-PD-1 therapy and the tHP value could not predict the clinical response. Interestingly, we found that median of plasma 10-7G values was significantly higher in responder group (p = 0.031, Figure 1A). When we focused on the utility of 10-7G values for distinguishing PD with ICI treatment, PD patients had significantly higher 10-7G values compared to patients with CR, PR, and SD (p = 0.0006, Figure 1B). We also confirmed the utility of 10-7G values for the predicting PD with ICI treatment (the area under the curve 0.816, Figure 1C). Accordingly, the overall survival rate was significantly correlated with the high 10-7G values (p = 0.0011). Conclusions: Plasma fucosylated haptoglobin levels represent a novel biomarker that reflects predicting clinical efficacy of ICIs in advanced RCC. SOURCE OF Funding: This work was supported by JSPS KAKENHI (Grant-in-Aid for Scientific Research (C), grant number 21K09343.
