Macrophage Biomarkers sCD163 and sSIRPα in Serum Predict Mortality in Sarcoma Patients

SIMPLE SUMMARY: About 40 percent of all patients treated with curative intent for a primary sarcoma will experience relapse; therefore, most patients do not survive. Prior studies implementing adjuvant chemotherapy have failed to increase survival rate. To increase the survival of sarcoma patients, differentiation of patients with poor versus good prognoses is essential. This study offers a prognostic profile that can identify patients with a very good prognosis who do not need additional treatment as well as patients with a very poor prognosis who need adjuvant treatment. Additionally, this study shows that the innate immune system is important in the prognosis of sarcoma patients, which could help facilitate an understanding of the lack of therapeutic response of checkpoint inhibitors in this group of patients. ABSTRACT: Most soft tissue sarcoma (STS) patients do not respond to traditional checkpoint inhibitor treatment, which may be due to infiltrating immunosuppressive tumour-associated macrophages. This study investigated the prognostic value of four serum macrophage biomarkers. Methods: Blood samples were taken from 152 patients with STS at the time of diagnosis; clinical data were prospectively collected. The concentrations of four macrophage biomarkers (sCD163, sCD206, sSIRPα, sLILRB1) were measured in serum, dichotomised based on median concentration, and evaluated either individually or when combined with established prognostic markers. Results: All macrophage biomarkers were prognostic of overall survival (OS). However, only sCD163 and sSIRPα were prognostic for recurrent disease (sCD163: hazard ratio (HR): 1.97 (95% CI: 1.10–3.51) and sSIRPα: HR: 2.09 (95% CI: 1.16–3.77)). A prognostic profile was made based on sCD163 and sSIRPα; it also included c-reactive protein and tumour grade. Patients with intermediate- or high-risk prognostic profiles (adjusted for age and tumour size) had a higher risk of recurrent disease compared to low-risk patients (HR: 2.64 (95% CI: 0.97–7.19)) and (HR 4.3 (95% CI: 1.62–11.47)), respectively. Conclusion: This study demonstrated that serum biomarkers of immunosuppressive macrophages were prognostic for OS; when combined with well-established markers of recurrence they allowed for a clinically relevant categorising of patients.