Novel Role for Tumor-Induced Expansion of Myeloid-Derived Cells in Cancer Cachexia

作者：Cuenca Alex G; Cuenca Angela L; Winfield Robert D; Joiner Dallas N; Gentile Lori; Delano Matthew J; Kelly Scumpia Kindra M; Scumpia Philip O; Matheny Michael K; Scarpace Philip J; Vila Lizette; Efron Philip A; LaFace Drake M; Moldawer Lyle L^*

来源：The Journal of Immunology, 2014, 192(12): 6111-6119.

DOI：10.4049/jimmunol.1302895

Cancer progression is associated with inflammation, increased metabolic demand, infection, cachexia, and eventually death. Myeloid-derived suppressor cells (MDSCs) commonly expand during cancer and are associated with adaptive immune suppression and inflammatory metabolite production. We propose that cancer-induced cachexia is driven at least in part by the expansion of MDSCs. MDSC expansion in 4T1 mammary carcinoma-bearing hosts is associated with induction of a hepatic acute-phase protein response and altered host energy and fat metabolism, and eventually reduced survival to polymicrobial sepsis and endotoxemia. Similar results are also seen in mice bearing a Lewis lung carcinoma and a C26 colon adenocarcinoma. However, a similar cachexia response is not seen with equivalent growth of the 66C4 subclone of 4T1, in which MDSC expansion does not occur. Importantly, reducing MDSC numbers in 4T1-bearing animals can ameliorate some of these late responses and reduce susceptibility to inflammation-induced organ injury and death. In addition, administering MDSCs from both tumor-and nontumor-bearing mice can produce an acute-phase response. Thus, we propose a previously undescribed mechanism for the development of cancer cachexia, whereby progressive MDSC expansion contributes to changes in host protein and energy metabolism and reduced resistance to infection.

• 出版日期2014-6-15