Abstract
Monocytic myeloid-derived suppressor cells (mMDSCs) are a class of immunosuppressive immune cells with prognostic value in many solid tumors. It is reported that the proportion of mMDSCs in the peripheral blood can be a predictive marker for response to cancer immunotherapy. In this study, we performed a correlation analysis of the proportion of mMDSCs in freshly-drawn peripheral blood, levels of plasma proteins, and demographic factors in colorectal cancer (CRC) patients, to find factors that could be used to predict mMDSC proportions. Freshly-drawn mMDSCs were measured using flow cytometry on peripheral blood mononuclear cells (PBMCs) from healthy donors (n = 24) and CRC patients (n = 78). The plasma concentrations of 29 different cytokines, chemokines, growth factors, and enzymes were measured using a multiplex assay or enzyme-linked immunosorbent assay. Correlation analysis to find mMDSC-associated factors was conducted using univariate and multivariate models. In univariate correlation analysis, there were no plasma proteins that were associated with mMDSC proportions in CRC patients. In multivariate analysis, considering all variables including age, sex, and plasma proteins, levels of inducible nitric acid synthase (iNOS) (p = 0.013) and platelet-derived growth factor (PDGF)-BB (p = 0.035) were associated with mMDSC proportion in PBMCs (mMDSC proportion [%] = 0.2929 - 0.2389 * PDGF-BB + 0.3582 * iNOS) (p < 0.005, r = 0.32). Measuring the plasma concentrations of iNOS and PDGF-BB may be useful in predicting the proportion of mMDSCs in CRC patients' peripheral blood. Further research is required to establish and validate these predictive factors. Data registration Patient data were registered in an anonymization system at Tsukuba Clinical Research & Development Organization (T-CReDO).
Highlights
Recent data have shown that there were approximately 1.1 million new colorectal cancer (CRC) cases and 551,269 CRC deaths worldwide in 2018 [1]
In agreement with previous reports, our current work has indicated that the proportion of Monocytic myeloid-derived suppressor cells (mMDSCs) in CRC patients was significantly higher than that in healthy donors
A significant difference was only observed between patients with advanced tumors and healthy donors while patients with stage I/II cancer had no significant increase in the proportion of circulating mMDSCs [19]
Summary
Recent data have shown that there were approximately 1.1 million new CRC cases and 551,269 CRC deaths worldwide in 2018 [1]. Previous studies have demonstrated that chronic inflammation is necessary for the initiation of CRC pathogenesis, and CRC-related inflammation promotes tumor development and progression through many different mechanisms, such as promoting angiogenesis and suppressing anti-tumor immune responses. A chronic inflammatory mucosal microenvironment can trigger oncogenic mutations that serve as CRC-initiating events [2]. Further tumor progression is induced by inflammatory immune cells, which work to turn an inflamed microenvironment into an immunosuppressive one [3]. It is reported that CRC induces inflammatory immune cell infiltrates through upregulation of “inflammatory signature” genes [2, 3]. The infiltration of CD4+ T cells and CD8+ T cells is associated with a good prognosis in CRC [4,5,6], immunosuppressive regulatory T cells and myeloid cells induce a poor prognosis [2, 3]; to characterize these immunosuppressive cells accurately is crucial for diagnosis and therapy of CRC
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