Using multicolor flow cytometry, the immunophenotype in the blood of renal cancer patients before and after tumor surgery was analyzed to identify surrogate markers for an immune monitoring. In earlier studies, we investigated activation-associated lymphocytic markers as well as monocytic markers, such as HLA-DR and CD13/aminopeptidase N [
8], while this study focused on the frequency of leukocytic subpopulations in blood, in particular on DC count. Pretreatment NLR as well as the granulocyte/DC ratio were used as surrogate markers for the immunophenotype. Comparing < pT3 stage RCC to ≥ pT3 tumor stages, higher leukocyte counts were detected in advanced tumor stages due to higher numbers of neutrophils. This is in line with investigations identifying a high neutrophil count as independent factor for poor prognosis in patients with metastatic RCC receiving IL-2 [
3] or anti-VEGF (vascular endothelial growth factor) agents [
9]. Tumors are known to both drive myelopoiesis, sometimes leading to a clinically apparent leukocytosis, and to inhibit the differentiation of myeloid cells resulting in the accumulation of immature myeloid cells [
10]. Cancer-associated myeloproliferation is not merely a paraneoplastic phenomenon of questionable importance, but leads to the suppression of host immunity and promotion of tumor angiogenesis. As an example, arginase-producing myeloid-derived suppressor cells have been revealed as a granulocytic subpopulation in RCC [
11].
A high pretreatment NLR is associated with poor prognosis for various cancers including RCC. Multivariate analysis identified increased NLR as an independent prognostic factor for overall, but neither for cancer-specific, nor for metastasis-free survival [
5]. In sunitinib-treated patients pre-treatment NLR has been discussed to be associated with progression-free survival [
12], and sunitinib even decreases NLR [
13]. Often, a NLR higher than 5 has been considered as a critical value correlating with poor prognosis in tumor patients [
14]. In our patient group a mean pretreatment NLR of 3.93 was found, with 8 out of 44 patients reaching NLR values higher than 5. However, NLR values showed a high variability (1.2 to 14.4), which prevented a significant difference between control group and tumor patients. Our results showed that combining the number of granulocytes with DC counts is a better approach to monitor immune depression in RCC patients, generating more pronounced differences than NLR. DC as cells specialized in antigen processing and presentation become potent stimulators of an adaptive immune response after undergoing the critical process of maturation. Blood DC represent only the 0.1–0.5% of leukocytes. Based on their lineage origin, they can be divided into two major subsets, plasmacytoid DC as the major producers of type I interferon and myeloid DC [
15]. The blood DC counts decrease not only with increasing age [
16], but diminished DC frequency and function was found in tumor disease, also in RCC patients [
17,
18]. It is noteworthy that the frequency of myeloid DC1 has been found to predict progression-free survival in patients with advanced RCC treated with sunitinib [
18]. Our results confirm the suitability of blood DC counts for an immune monitoring, and the granulocyte/DC ratio raises differences between RCC patients and control group, or between different tumor stages.
Distinct peri-operative changes have been described in RCC patients, e.g. a down-regulated intensity of monocytic HLA-DR molecules [
8]. Granulocytes increase post-operatively and lymphocyte counts decrease, therefore NLR increases at the first postoperative day with higher values in the open surgery group. DC counts decreased after surgery resulting in a raising granulocyte/DC ratio. This marker stayed at high level in the “open surgery” group for the whole observation period of one week, whereas the marker reversed within short time in the laparoscopy group, an observation, which needs further investigation. Understanding the dynamics of DC release and vascular distribution would provide key insights into the process of immune suppression and reconstitution after tumor surgery.