The effect of l-arginine supplementation and surgical trauma on the frequency of myeloid-derived suppressor cells and T lymphocytes in tumour and blood of colorectal cancer patients

Abstract

Purpose: l-arginine (L-arg) deficiency causes immunosuppression, but it is unknown if L-arg supplementation in colorectal cancer (CRC) patients restores immune system activity. Our objective was to investigate the effect of L-arg supplementation on the frequency of monocytic (M) and polymorphonuclear (PNM) myeloid-derived suppressor cells (M-MDSCs and PMN-MDSCs, respectively).

Methods: We enrolled 65 CRC patients (34 males, 31 females) aged 69 ​± ​10 years into a prospective, randomised, double-blind study. Twenty-eight patients received L-arg and 37 received placebo for 9 days at a dose of 10 ​g/day. The frequency changes in MDSC, CD4⁺ cells and the concentration of C-reactive protein (CRP) were assessed before supplementation with L-arg (test 1), after 9 days of supplementation (test 2), and after surgery on day 11 (test 3).

Results: The frequency of M-MDSC in the tumours of patients receiving L-arg supplementation was higher than in placebo-treated patients, as was the frequency of PMN-MDSC and M-MDSC in the mucosa. CRP concentration in the serum of placebo-treated patients in test 2 was higher than in test 1, and the concentration in the serum of patients with L-arg supplementation in test 2 was lower than in test 1. Moreover, the expression pattern of the argininosuccinate synthase 1 (ASS1) suggests that CRC is not auxotrophic for L-arg.

Conclusions: The results of this study do not support the hypothesis that L-arg supplementation in CRC patients can reduce immunosuppression by decreasing the frequency of suppressor cells and increasing the frequency of effector CD4⁺ T cells.

Keywords: Colorectal cancer; Myeloid-derived suppressor cells; Non-auxotrophic tumours; l-arginine supplementation.