Parabiosis Suppresses Breast Tumor Growth With Increased Effector Memory T Cells and HSPB3

Parabiosis, a model involving shared circulation between two organisms, enables the investigation of systemic immune factors in tumor biology. This study aimed to evaluate whether breast tumor growth is suppressed in naïve mice following parabiosis with tumor-bearing mice and to identify associated immune cell changes and circulating anti-tumor factors.

Parabiosis was established between breast tumor-bearing mice and naïve mice. After 28 days, parabionts were surgically separated, and naïve mice were inoculated with breast tumor cells. Tumor growth was monitored for 14 days. Immune cell populations were analyzed using flow cytometry, and serum proteins were profiled using liquid chromatography-mass spectrometry (LC-MS) followed by validation with enzyme-linked immunosorbent assay (ELISA). Functional effects of candidate proteins were assessed in vitro using cell viability and caspase-3/-7 assays.

Naïve mice previously subjected to parabiosis exhibited significantly reduced tumor growth compared to control mice. This effect was associated with increased proportions of effector memory CD4⁺ and CD8⁺ T cells in the spleen, without significant changes in regulatory T cells or B cell subsets. Proteomic analysis revealed distinct serum protein profiles, with elevated levels of heat shock protein beta-3 (HSPB3). Recombinant HSPB3 reduced breast tumor cell viability and increased caspase-3/-7 activity in vitro in a dose-dependent manner.

Parabiosis with tumor-bearing mice confers anti-tumor effects in naïve mice, characterized by enhanced effector memory T cell responses and increased circulating HSPB3. These findings suggest that parabiosis is a useful platform for identifying systemic anti-tumor immune mechanisms and circulating therapeutic targets in breast cancer.