Urologic Oncology: Seminars and Original Investigations
Seminars ArticleMyeloid-derived suppressors cells (MDSC) correlate with clinicopathologic factors and pathologic complete response (pCR) in patients with urothelial carcinoma (UC) undergoing cystectomy
Introduction
Bladder cancer is the most common cancer of the urinary tract with urothelial carcinoma (UC) as its most common histologic type [1]. Approximately 20% to 40% of patients have muscle-invasive urothelial carcinoma (MIUC) either at initial diagnosis or following progression from a previously non–muscle-invasive tumor state [2]. Radical cystectomy and bilateral pelvic lymph node (LN) dissection remains the standard treatment for most patients with nonmetastatic MIUC, and neoadjuvant cisplatin-based chemotherapy improves long-term survival compared to patients undergoing surgery alone [3].
The clinical and pathological features at the time of cystectomy can be prognostic for disease recurrence and long-term outcomes for patients with MIUC. In particular, the presence of lymph node (LN) involvement, higher tumor stage, and lymphovascular invasion (LVI) are poor prognostic factors [4], [5]. Conversely, a complete pathological response (pCR) following cystectomy predicts for improved progression-free survival and overall survival (OS) [6], [7], [8], [9]. To date, limited biomarkers exist to predict surgical pathological outcomes at the time of cystectomy [10]. Such data could be useful in a variety of settings including potentially favoring a bladder-sparing definitive therapy or guide future surveillance approaches instead of radical cystectomy for patients who have a pCR to neoadjuvant chemotherapy [11], [12], [13], [14], [15].
Myeloid derived suppressor cells (MDSCs) are a phenotypically diverse population of bone marrow-derived cells that play an important role in tumor progression based on their immunosuppressive and proangiogenic properties [16]. Circulating MDSCs have been shown to correlate with stage, tumor burden, treatment response, and clinical outcomes in a variety of cancers [17], [18], [19]. Circulating MDSC subsets have been previously shown to be highly proliferating and activate a host of proinflammatory cytokines in patients with bladder cancer [20]. In this study, the correlation between blood and tissue MDSCs, clinicopathologic features, and neoadjuvant treatment outcomes in patients with MIUC undergoing radical cystectomy was investigated.
Section snippets
Patients
Patients with UC of the bladder who were scheduled to undergo cystectomy were all consented on an IRB approved protocol (Cleveland Clinic IRB 14–1222, approval date February 12, 2015) for blood and tissue collection prior to surgery. All surgical patients were considered for inclusion regardless of prior intravesical therapy or neoadjuvant chemotherapy. Patients with metastatic disease at the time of surgery were excluded from the analysis, with the exception of patients with only regional
Patient characteristics
Overall, 85 patients who underwent cystectomy for UC between February 25, 2015 and December 22, 2016 were included in the analysis. All patients had blood drawn for analysis and 23 patients had available residual tumor tissue collected for analysis at the time of surgery. Most of the patients (91%, n = 77) had blood drawn within 3 days of surgery; only 8 patients had blood drawn between 4 and 15 days prior to surgery.
Of the 85 patients, 74 (87%) were men with median age at diagnosis of 68
Discussion
MDSCs are immunosuppressive cells that have predictive and prognostic roles in patients with solid tumors [17], [19]. Limited data is published regarding the role of circulating and tissue MDSCs in patients with UC. The fundamental findings of this study are that specific subsets of MDSCs correlate with clinicopathologic features at the time of cystectomy in patients with MIUC undergoing cystectomy. Specifically, this study highlights that there are significant associations between circulating
Conclusions
In conclusion, blood and tissue MDSC levels correlate with several clinicopathologic factors and are associated with pCR. Future studies are needed to highlight the role and function of MDSC in predicting long-term outcomes and to determine the clinical implications of these findings.
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