Potential role of immunological factors in early diagnosis of cancer cachexia in C26 tumor-bearing mice

Jae Eun Ju,Mi-Sook Kim,Mi So Lee,Namhyun Chung,Ji Young Lee,Youn Kyoung Jeong,Joo Hyun Kang,Eun Ho Kim

doi:10.1186/s13765-019-0417-5

Abstract

Cachexia is a wasting syndrome associated with high mortality in cancer patients through inducing the failure of normal metabolism and reducing the efficacy of cancer treatment. Thus, it is critically important to diagnose cancer cachexia early. To provide background data for the diagnosis of cachexia, cancer cachectic factors were characterized in the present situation, including immunological cachectic changes during cachexia progression in a cancer cachexia mouse model. Major constitution of cachexia progression is known as the stages of pre-cachexia, cachexia, and refractory cachexia. In the pre-cachexia stage, the weights of immune-related organs, including the thymus and spleen were significantly. T cell populations in spleen were markedly reduced and cachectic cytokines consistently increased in a time-dependent manner. Immunosuppression by activation of cytotoxic T-lymphocyte-associated antigen 4 was induced earlier in CD4+ cells versus other T cell populations. Furthermore, monocyte chemoattractant protein 1 and interleukin-6 levels in the cachexia group were significantly increased at 3 days from C26 cell inoculation whereas significant carcass weight loss as a classical diagnostic marker occurred at 9 days from C26 cell inoculation. In conclusion, the initiation of cachectic immunological changes was observed prior to weight loss, during the pre-cachexia stage. Accordingly, these findings reveal that the monitoring of humoral and immunological factors may be more sensitive than weight loss for the initial diagnosis and treatment of cachexia.

Highlights

Cancer patients with progressive cachexia suffer severe morbidity and a high mortality rate (~ 20%) [1]
According to the classical cachexia diagnosis that 5% body weight loss is lead by cachexia progression [4], we terminated experiment at 21 days after C26 cell inoculation when body weight of mice decreased by 5%
The expression of immune checkpoint markers on cells from the cachexia group was lower than in the normal group (Fig. 2b). These results demonstrate that T cells were depleted to a greater extent than natural killer (NK) and dendritic cells (DCs) cells during in refractory cachexia, whereas no immunosuppression by activation of immune checkpoint markers on T cells was observed

Summary

Introduction

Cancer patients with progressive cachexia suffer severe morbidity and a high mortality rate (~ 20%) [1]. Cachexia directly affects the survival rate by inducing the failure of normal metabolism, leading to conditions such as hypogonadism, insulin resistance, and inflammation [2]. Cancer cachexia is difficult to treat and may eventually lead to death. Immunosuppression could occur when immune cells are reduced and/or affected by inhibitory signals such as immune checkpoints molecules including T-lymphocyte-associated antigen 4 (CTLA4) and programmed cell death protein 1 (PD-1) [11]. Immunotherapy against cancer has focused on overcoming the immunosuppression of immune cells by improving immunological activity and inhibiting these immune checkpoints [12, 13]

Methods

Results

Conclusion