Abstract
Cachexia affects about 80% of gastrointestinal cancer patients. This multifactorial syndrome resulting in involuntary and continuous weight loss is accompanied by systemic inflammation and immune cell infiltration in various tissues. Understanding the interactions among tumor, immune cells, and peripheral tissues could help attenuating systemic inflammation. Therefore, we investigated inflammation in the subcutaneous adipose tissue and in the tumor, in weight stable and cachectic cancer patients with same diagnosis, in order to establish correlations between tumor microenvironment and secretory pattern with adipose tissue and systemic inflammation. Infiltrating monocyte phenotypes of subcutaneous and tumor vascular-stromal fraction were identified by flow cytometry. Gene and protein expression of inflammatory and chemotactic factors was measured with qRT-PCR and Multiplex Magpix® system, respectively. Subcutaneous vascular-stromal fraction exhibited no differences in regard to macrophage subtypes, while in the tumor, the percentage of M2 macrophages was decreased in the cachectic patients, in comparison to weight-stable counterparts. CCL3, CCL4, and IL-1β expression was higher in the adipose tissue and tumor tissue in the cachectic group. In both tissues, chemotactic factors were positively correlated with IL-1β. Furthermore, positive correlations were found for the content of chemoattractants and cytokines in the tumor and adipose tissue. The results strongly suggest that the crosstalk between the tumor and peripheral tissues is more pronounced in cachectic patients, compared to weight-stable patients with the same tumor diagnosis.
Highlights
Cachexia is a multifactorial and multi-organ syndrome characterized by continuous and involuntary weight loss and by systemic inflammation [1, 2]
Informed body mass and current body mass, marked weight loss was found for cancer patients (CC), in relation to the weight-stable cancer (WSC) group, in accordance with the proposed by Evans et al [19]
We found that gene expression of TNF-α, IL-1β, and MCP-1/CCL2 were significantly higher in cachectic cancer patients when compared with WSC
Summary
Cachexia is a multifactorial and multi-organ syndrome characterized by continuous and involuntary weight loss and by systemic inflammation [1, 2]. This syndrome was described about 2000 years ago by Hippocrates and is a common feature of several diseases, such as chronic obstructive pulmonary disease, chronic heart failure, chronic infection, and cancer [3]. An important feature of cachexia is chronic systemic inflammation and, paradoxically, immunosuppression [7] Mediators produced by both the tumor and the host induce intracellular changes directly associated with persistent inflammation [8]. An intricate tumor–host interaction is established, promoting an imbalance that favors the pro-inflammatory over the anti-inflammatory status [10, 11]
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