Triple-Negative Breast Cancer Cells Resist Natural Killer Cell-Mediated Killing Through Interleukin-11 Trans-Signaling.

ABSTRACT: Natural killer (NK) cell-based therapies show great promise for treating triple-negative breast cancer (TNBC). However, in the tumor microenvironment, some TNBC cells develop resistance to NK cell-mediated killing and contribute to NK cell exhaustion. In this study, TNBC cell populations are isolated that can resist NK cell attacks and uncovered the underlying mechanisms. It is found that these resistant TNBC cells secrete high levels of interleukin-11 (IL-11). IL-11 acts through a process known as trans-signaling by forming complexes with the soluble IL-11 receptor (sIL-11R) and engaging the gp130 receptor on NK cells. This trans-signaling activates the JAK1/STAT1/3 pathway, leading to the upregulation of p21 and subsequent cell cycle arrest in NK cells. As a result, the proliferation and

SUBMITTER: Yang H 

PROVIDER: S-EPMC12822480 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature