P10: The subsets of peripheral blood monocytes in cancer patients

Abstract

Background Tumour-associated macrophages (TAM) derived from peripheral blood monocytes are a key immune regulatory component of tumour microenvironment (Qian, Pollard, 2010). Advanced clinically applicable strategy for TAM targeting is their functional reprogramming (Wynn et al., 2013). Monocytes/macrophages are heterogeneous and versatile cells. Two major macrophage subpopulations with different functions which represent extreme of a continuum in a universe of activation states, including classically activated/inflammatory (M1) and alternatively activated/regenerative (M2) macrophages, have long been recognized (Zhou et al., 2014). CD68 and CD163 are the general markers of M1 and M2 subsets respectively (Hoene et al., 2015, Tedesco et al., 2014). However, there are different markers expressed on surface of monocytes/macrophages that reflected some special functional activities of these cells. Thus, expression of CD119(IFN-γR) or CD124(IL-4R) reflects the predisposition to M1 or M2-polarisation by suitable cytokines IFN-γ and IL-4 (Tedesco et al., 2014). The pro-inflammatory marker CD282 (TLR2) is associated with antibacterial function. Anti-inflammatory CD36+ cells take part in scavenging of apoptotic remains and inducing IL-10 production. Although monocytes/macrophages could undergo their phenotypically/functionally dynamic switch in response to the microenvironment signals there is some predisposition of their status in peripheral blood to polarization in tissues. Modulation of monocyte peripheral status before their infiltration is an attractive target for cancer therapeutic approaches. The aim is to study phenotypic subsets of peripheral blood monocytes in breast and gastric cancer patients. Materials and methods 8 breast cancer and 8 gastric cancer patients T1N0-3M0 treated in Tomsk Cancer Institute were enrolled in investigation. The diagnosis was histologically verified. Phenotypic features were assessed by flow cytometry using mAb CD119(IFN-γRα), CD124(IL-4R), CD282 (TLR2), CD36, CD68, CD163 (BD Pharmingen) before treatment and in 5 days after surgery of tumour. Results We found that amounts of monocytes expressing main surface markers of M-1 or M2-type activation in peripheral blood in cancer patients wasn’t large: CD68+ and CD163+ cells were 4.18 ± 3.41% and 7.64 ± 3.75% of whole pool of monocytes respectively. This finding supports the fact that in general M1/M2-polarization of monocytes/macrophages occurs in local tissues by specific micro- environmental conditions [Ambarus et al., 2012, Zhou et al., 2014]. But high levels of CD119(IFN-γR)+monocytic cells (87.36 ± 12.08%) in peripheral blood showed that predisposition to M1-polarization of circulating monocytes exists in cancer patients, because it’s known IFN-γ significantly increased the fraction of surface CD68 – expressing cells and down-regulated expression of the M2 markers in vitro [Tedesco et al., 2014]. Expression of CD124 (IL-4R) was detected only in 26.81 ± 8.11% of monocytes in cancer patients. The subset of pro-inflammatory CD282+ (TLR2) circulating monocytes amounted 64.38 ± 9.47% of total count of monocytic cells. Anti-inflammatory CD36+ monocytes were 35.66 ± 7.00%. It is noteworthy this subset was 48.43 ± 8.13% in breast cancer patients and only 22.88 ± 9.86% in gastric cancer patients (p On the 5-th day after surgery, we detected decrease in CD282+ cells from 80.90 ± 8.55% to 38.70 ± 9.47% of total monocytes count in breast cancer patients (p Conclusion There were a small accounts of M1 (CD68+) or M2 (CD163+) polarized monocytes in peripheral blood in breast and gastric cancer patients. INF-γ(CD119)+ and CD282(TLR2)+ pro-inflammatory subsets were dominated in cancer patients. The high levels of CD36+monocytes was the feature of breast cancer patients as compared with gastric cancer ones. Surgery removal of tumour was associated with increasing of CD36+ monocytes in both breast and gastric cancer and with decreasing of CD282 (TLR2)+ monocytes in breast cancer.