Internalization of extracellular vesicles of cancer patients by peripheral blood mononuclear cells during polychemotherapy: connection with neurotoxicity

Abstract

Extracellular vesicles (EVs), exhibiting their functional activity after internalization by recipient cells, are involved in the pathogenesis of drug-induced polyneuropathy (DIPN), a common complication of antitumor therapy. In this work, the internalization of EVs obtained from colorectal cancer patients undergoing polychemotherapy and its relationship with neurotoxicity were assessed using a model system of mononuclear leukocytes. Circulating EVs were isolated from 8 colorectal cancer patients who received antitumor therapy according to the FOLFOX or XELOX regimens before the start of chemotherapy (point 1) and after 3–4 courses (point 2). Mononuclear leukocytes of a healthy donor served as a cellular model system for EV internalization in vitro. EV internalization was assessed using fluorescence microscopy. It was shown that internalization of EVs obtained from colorectal cancer patients with high neurotoxicity was higher than in the group with low neurotoxicity. The ability of CD11b-positive (CD11b⁺) and CD11b-negative (CD11b⁻) mononuclear leukocytes of a healthy donor to internalize EVs obtained from patients before and after chemotherapy did not reveal significant differences. A direct relationship was found between the relative number of CD11b⁻ cells with internalized EVs and the integral index of neurotoxicity according to the NRS scale at the peak of its manifestation (point 2) (r=0.675, p