作者
Camille Jacques,Irene Marchesi,Francesco Paolo Fiorentino,Flora Marchand,Mathias Chatelais,Ilaria Floris
摘要
Tumor-associated macrophages (TAMs) play a pivotal role in cancer regulation by influencing tumor growth, metastasis, and the immune microenvironment. By providing low doses and ultra-low doses (ULD) of immune regulators to the organism, micro-immunotherapy (MI) medicines (MIM) could be seen as valuable adjuvant drugs in the context of a wide range of pathological conditions, including cancers. Thus, these MIM could target TAMs, affecting their phenotype and activities. In this study, the anti-tumor and the immune-stimulatory effects of four capsules out of the ten composing the Labo’life’s MIM 2LC1® (2LC1-1, 2LC1-6, 2LC1-7, and 2LC1-8), as well as the specific nucleic acid (SNA®) sequence SNA-MYC present at ULD in this medicine have been evaluated in vitro, in several cancer models, and in human monocyte-derived macrophages. Our results showed that the tested MI formulations increased the tumor cell death of spheroids from HCT-116 colon cancer cells, while reducing the spheroid volume. Moreover, the treatments impaired the clonogenic capabilities of two cancer cell lines from epithelial origin, the LNCaP prostate cancer and the MCF-7 breast cancer cells. Interestingly, ULD of the SNA-MYC shared similar anti-cancer capabilities in those models, and it led to a significant reduction in the expression of C-MYC when evaluated in a model of human M2 macrophages. In the same model, the MI formulations also increased the expression of CD86 and HLA-DR, two markers of M1 anti-tumor macrophages. In addition, the tested items modulated the secretion of a panel of chemokines related to macrophage activity and immune cell recruitment. Finally, our results showed that 2LC1-8 increased the phagocytosis capabilities of human monocyte-derived macrophages, thus possibly contributing to sustaining the immune functions of M1, which are crucial in the context of cancer. Even if more research is needed to uncover their exact mechanism of action, these results suggest that the tested capsules of 2LC1 as well as ULD of SNA-MYC display both anti-tumor and immune-enhancing effects.