Selection of tumor ‑resistant variants following sustained natural killer cell‑mediated immune stress.

Selection of tumor‑resistant variants following sustained natural killer cell‑mediated immune stress. Oncol Rep. 2020 Nov 27;: Authors: Carré T, Thiery J, Janji B, Terry S, Gros G, Meurice G, Kieda C, Olive D, Chouaib S Abstract Resistance of tumor cells to cell‑mediated cytotoxicity remains an obstacle to the immunotherapy of cancer and its molecular basis is poorly understood. To investigate the acquisition of tumor resistance to cell‑mediated cytotoxicity, resistant variants were selected following long‑term natural killer (NK) cell selection pressure. It was observed that these variants were resistant to NK cell‑mediated lysis, but were sensitive to autologous cytotoxic T lymphocytes or cytotoxic drugs. This resistance appeared to be dependent, at least partly, on an alteration of target cell recognition by NK effector cells, but did not appear to involve any alterations in the expression of KIR, DNAM1 or NKG2D ligands on resistant cells, nor the induction of protective autophagy. In the present study, in order to gain further insight into the molecular mechanisms underlying the acquired tumor resistance to NK cell‑mediated cytotoxicity, a comprehensive analysis of the variant transcriptome was conducted. Comparative analysis identified an expression profile of genes that best distinguished resistant variants from parental sensitive cancer cells, with candidate genes putatively involved in NK cell‑mediated lysis ...
Source: Oncology Reports - Category: Cancer & Oncology Tags: Oncol Rep Source Type: research