Interleukin-7 enhances anti-tumor activity of CD8+ T cells in patients with hepatocellular carcinoma

Abstract

Interleukin (IL)-7 stimulation improves virus- and tumor-specific CD8⁺ T cell responses. However, the role of IL-7 in modulation of dysfunctional CD8⁺ T cells in hepatocellular carcinoma (HCC) was not completely understood. In this study, a total of 37 HLA-A2 restricted patients with HCC and 16 healthy individuals were enrolled. IL-7 expression and its receptor α chain CD127 level was measured. The regulatory activity of IL-7 to peripheral and liver-resident CD8⁺ T cells was investigated in co-culture systems which were directly or indirectly contacted with HCC cell line HepG2 in vitro. Serum IL-7 concentration was significantly reduced in HCC patients, while effective anti-tumor treatment up-regulated IL-7 expression. However, CD127 expression was comparable on peripheral CD8⁺ T cells from either HCC patients and healthy individuals, and was also similar on liver-resident CD8⁺ T cells from either normal tissues and HCC specimens. CD8⁺ T cells purified from normal liver tissues also presented stronger cytotoxicity compared with those from HCC specimens prior to and post IL-7 treatment. Moreover, IL-7 stimulation not only augmented cytotoxicity of peripheral and liver-resident CD8⁺ T cells, but also promoted IFN-γ and TNF-α production by CD8⁺ T cells in direct contact co-culture system. This process was accompanied by down-regulation of programmed death-1 (PD-1) expression on CD8⁺ T cells. Our present data indicated that IL-7 enhanced both cytolytic and noncytolytic activity of CD8⁺ T cells to HCC probably via repression of PD-1 under direct tumor cells presentation. IL-7 might be considered as one of the therapeutic candidates for HCC treatment.

Keywords: CD8(+) T cells; Hepatocellular carcinoma; Immunoregulation; Interleukin-7.