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Microwave ablation of primary breast cancer inhibits metastatic progression in model mice via activation of natural killer cells.

ABSTRACT: Surgery is essential for controlling the symptoms and complications of stage IV breast cancer. However, locoregional treatment of primary tumors often results in distant progression, including lung metastasis, the most common type of visceral metastasis. As a minimally invasive thermal therapy, microwave ablation (MWA) has been attempted in the treatment of breast cancer, but the innate immune response after MWA has not yet been reported. Using two murine models of stage IV breast cancer, we found that MWA of primary breast cancer inhibited the progression of lung metastasis and improved survival. NK cells were activated after MWA of the primary tumor and exhibited enhanced cytotoxic functions, and the cytotoxic pathways of NK cells were activated. Depletion experiments showed that NK cells but not CD4+ or CD8+ T cells played a pivotal role in prolonging survival. Then, we found that compared with surgery or control treatment, MWA of the primary tumor induced completely different NK-cell-related cytokine profiles. Macrophages were activated after MWA of the primary tumor and produced IL-15 that activated NK cells to inhibit the progression of metastasis. In addition, MWA of human breast cancer stimulated an autologous NK-cell response. These results demonstrate that MWA of the primary tumor in metastatic breast cancer inhibits metastatic progression via the macrophage/IL-15/NK-cell axis. MWA of the primary tumor may be a promising treatment strategy for de novo stage IV breast cancer, although further substantiation is essential for clinical testing.

SUBMITTER: Yu M

PROVIDER: S-EPMC8429677 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Recent reports suggest that Natural Killer (NK) cells may modulate pathogenesis of primary HIV-1 infection. However, HIV dysregulates NK-cell responses. We dissected this bi-directional relationship to understand how HIV impacts NK-cell responses during primary HIV-1 infection.Paired samples from 41 high-risk, initially HIV-uninfected CAPRISA004 participants were analysed prior to HIV acquisition, and during viraemic primary HIV-1 infection. At the time of sampling post-infection five women were seronegative, 11 women were serodiscordant, and 25 women were seropositive by HIV-1 rapid immunoassay. Flow cytometry was used to measure NK and T-cell activation, NK-cell receptor expression, cytotoxic and cytokine-secretory functions, and trafficking marker expression (CCR7, ?(4)?(7)). Non-parametric statistical tests were used. Both NK cells and T-cells were significantly activated following HIV acquisition (p?=?0.03 and p<0.0001, respectively), but correlation between NK-cell and T-cell activation was uncoupled following infection (pre-infection r?=?0.68;p<0.0001; post-infection, during primary infection r?=?0.074;p?=?0.09). Nonetheless, during primary infection NK-cell and T-cell activation correlated with HIV viral load (r?=?0.32'p?=?0.04 and r?=?0.35;p?=?0.02, respectively). The frequency of Killer Immunoglobulin-like Receptor-expressing (KIR(pos)) NK cells increased following HIV acquisition (p?=?0.006), and KIR(pos) NK cells were less activated than KIR(neg) NK cells amongst individuals sampled while seronegative or serodiscordant (p?=?0.001;p<0.0001 respectively). During HIV-1 infection, cytotoxic NK cell responses evaluated after IL-2 stimulation alone, or after co-culture with 721 cells, were impaired (p?=?0.006 and p?=?0.002, respectively). However, NK-cell IFN-y secretory function was not significantly altered. The frequency of CCR7+ NK cells was elevated during primary infection, particularly at early time-points (p<0.0001).Analyses of immune cells before and after HIV infection revealed an increase in both NK-cell activation and KIR expression, but reduced cytotoxicity during acute infection. The increase in frequency of NK cells able to traffic to lymph nodes following HIV infection suggests that these cells may play a role in events in secondary lymphoid tissue.

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Microwave ablation of primary breast cancer inhibits metastatic progression in model mice via activation of natural killer cells.

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