Osteoclasts affect the anti-cancer activity of NK cells

Area of Science:

• Immunology
• Oncology
• Cell Biology

Background:

• Non-small cell lung cancer stem cells (NSCLC CSCs) drive bone metastasis by interacting with osteoclasts (OCs) and creating an immunosuppressive bone microenvironment.
• Natural killer (NK) cells are crucial immune cells that can eliminate cancer cells.

Purpose of the Study:

• To investigate the interaction among OCs, IL-15-stimulated NK cells, and NSCLC CSCs.
• To determine if NK cells can interfere with the pro-metastatic crosstalk between OCs and NSCLC CSCs.

Main Methods:

• In vitro co-cultures of OCs, NK cells, and NSCLC CSCs derived from the A549 cell line were established on plastic and bone slices.
• OC activity was assessed by tartrate-resistant acid phosphatase (TRAP) quantification and resorption area measurement.
• NK cell phenotype, receptor/ligand expression, and degranulation activity (CD107a) were analyzed via flow cytometry.

Main Results:

• OCs co-cultured with NK cells and NSCLC CSCs showed decreased TRAP activity and resorption.
• NK cells, surprisingly, promoted NSCLC CSC adhesion and growth on bone slices.
• Co-culture with OCs and/or NSCLC CSCs led to NK cell exhaustion, characterized by increased inhibitory receptors (TIGIT, TIM3) and reduced degranulation.

Conclusions:

• Osteoclasts negatively impact NK cell cytotoxic activity, thereby facilitating the growth of NSCLC CSCs in bone.
• This study uncovers a novel role for OCs in modulating the immune microenvironment by suppressing NK cell function, contributing to NSCLC bone metastasis.