Radium-223 dichloride causes transient changes in natural killer cell population and cytotoxic function

Area of Science:

• Immunology
• Radiobiology
• Oncology

Background:

• Natural killer (NK) cells are crucial for innate and adaptive immunity.
• The effects of chronic high-linear energy transfer (LET) alpha particle exposure from radionuclides on NK cells are not well understood.
• Previous research focused on ionizing radiation's impact on NK cell cytotoxicity, but not specifically on alpha particle emitters like ²²³RaCl₂.

Purpose of the Study:

• To investigate the effects of ²²³RaCl₂ on the population size and function of splenic NK cells.
• To determine how chronic alpha particle exposure influences NK cell activity in vivo.
• To identify potential therapeutic windows for combining ²²³RaCl₂ with other immunotherapies.

Main Methods:

• Swiss Webster mice received intravenous injections of 0, 50, or 600 kBq/kg of ²²³RaCl₂.
• Spleens were collected at 5, 12, and 19 days post-injection for analysis.
• Flow cytometry assessed splenocyte subpopulations (B, T cells, NK cells), and NK cell function was measured using the ⁵¹Cr-release assay with YAC-1 target cells.

Main Results:

• The total splenocyte count remained unaffected by ²²³RaCl₂ administration.
• Significant alterations were observed in NK cell and CD8 T lymphocyte distribution.
• NK cell functional activity showed a substantial increase at 12 days post-administration but a marked decrease by day 19.

Conclusions:

• ²²³RaCl₂ modulates NK cell functional activity, with effects varying based on administered dose and time post-administration.
• The observed biphasic effect (enhancement followed by diminution) suggests a dynamic interplay between ²²³RaCl₂ and NK cell responses.
• These findings indicate a potential optimal time frame for utilizing ²²³RaCl₂-induced NK cell responses in conjunction with other cancer therapies.