Multiple immunological mechanisms of cancer cachexia in patients with solid tumors.

Abstract

667 Background: Cancer cachexia is a mixed and multiple factorial condition and commonly seen in patients with advanced cancer, and has long been reported that host-immune function is critically participated. Chronic inflammation plays a key role in the progress of malignant diseases and has been reported to relate with immune suppression and nutritional impairment seen in patients with advanced diseases. Methods: Peripheral blood mononuclear cells (PBMC) were collected from 18 normal healthy volunteers and 112 patients with gastrointestinal cancer. These cells were used for the detection of MDSC (myeloid-derived suppressor cells: CD11b+CD14-CD33+) by flow cytometry. PBMC was also used for the PHA-blastogenesis of lymphocytes which is a marker of cell mediated immunity (stimulation indices: SI) and for the production assay of cytokines including IFN-G, IL-6 and IL-10. Serum levels of soluble cytokine receptors including sIL-2R and sTNF-R1, and anti-inflammatory molecules such as IL-10 and IL-1 receptor antagonist (IL-1RA) were also measured. For the evaluation of nutritional status, serum concentrations of rapid turnover protein (RTP) including prealbumin, transferrin and retinol binding protein was measured. NLR (neutrophil/lymphocyte ratio) was calculated and used as a marker of chronic inflammation. Results: The circulating levels of MDSC was significantly increased in esophageal, gastric and colorectal carcinomas than in normal volunteer and significantly inversely correlated with serum concentration of RTP and with SI, and correlated with markers for inflammation. The levels of sIL-2R and sTNF-R1 were increased in patients with gastric and colorectal and inversely correlated with the levels of RTP and SI. In patients with cachexia, serum concentrations of IL-10 were increased and the production of IFN-G was decreased. Conclusions: It is suggested that suppression of cell-mediated immune function exists in patients with cancer cachexia and the immunological mechanisms of nutritional damages in these patients are even partially driven by Th2-dominant condition of CD4(+) cells and MDSC. These complicated mechanisms are also involved in inflammation-related immunological condition such as SIRS and CARS.