Biotroy Therapeutics Collaborates to Publish Research Findings on New Tumor Treatment Target Galectin-8

Cancer immunotherapy is a treatment method that utilizes the immune system to enhance its ability to attack cancer. It aims to activate, enhance, or repair the patient's own immune system, enabling it to recognize, attack, and eliminate cancer cells. Immune checkpoint inhibitors, such as anti-PD-1 and anti-CTLA-4 antibodies, work by inhibiting negative regulatory signals on immune cells, thus activating and enhancing the attack function of T cells and enhancing the immune system's response to cancer. Despite significant progress in tumor immunotherapy with PD-1/PD-L1 targeting treatments, the overall effective response rate is around 30%, leaving many patients without benefit. Therefore, discovering new drug targets has become a major research direction, and the development of innovative drugs is poised for rapid advancement. In recent years, attention has also been given to other cell groups beyond T cells, such as Myeloid-Derived Suppressor Cells (MDSCs), which play a role in inducing and maintaining immune suppression in the tumor microenvironment.

Recently, the research team of Shanghai BioTroy Therapeutics in collaboration with the Xu Jie research group of Fudan University and others published a research paper in Am J Cancer Res“Galectin-8 alters immune microenvironment and promotes tumor progression”。

　　Galectin-8 (Gal-8), encoded by LGALS8 gene, is a unique member of the Galectin family. Widely expressed in tumors, Galectin-1, -3, -7, -8, and -9 are among the primary molecular mechanisms by which tumors evade immune control. Among these, Gal-1, -3, and -9 have already been established in the field of tumor immunotherapy.Firstly,MC38, a C56BL/6-derived colon cancer cell line, was transfected with plasmid to construct a stable Gal-8 overexpressing cell line. Overexpression (OE) and wildtype (WT) cells were injected subcutaneously into wildtype (WT) C56BL/6J mice,Specifically, 1.5e6 MC38 cells were injected per individual on day 0. The subcutaneous tumors were detectable in most of the mice from day 7. Since then, tumors were measured three times a week until the tumor size was not ethically acceptable. Over time, the Gal-8 OE tumors grew faster than the WT tumor.After mice were sacrificed on day 28, dissected tumors were photographed in vivo and ex vivo.The statistical comparison showed that tumors with high Gal-8 expression at 28 days overgrew that of the wildtype.(Figure 1)

Figure1 Galectin-8 promotes tumor progression in vivo

For the mice model, peripheral blood mononuclear cells (PBMCs) were sampled for Flow cytometry in order to gate and measure the level of M-MDSC cells, defined as CD11b+, Ly-6C+, Ly-6G- cells (Figure 2A). As a result, the Gal-8 OE group presented the highest level of M-MDSCs (Figure 2B). Tumors were dissected and sliced to evaluate tumor-infiltrating immune status. IHC staining of CD8 and FoxP3 was performed on tumor samples (Figure 2C) to show that Gal-8 upregulated FoxP3 positive T regulator cells (Tregs) level and downregulated CD8+ T cell infiltration in MC38 tumors (Figure 2D,2E)

Figure 2 Galectin-8 alters the tumor microenvironment

Additionally, to analyze the related tumor-infiltrating factors in cancer and the expression of Gal-8 in different tumor tissues, a bioinformatics analysis was conducted using public databases. LGALS8 was demonstrated to negatively correlate with active CD8+ T lymphocytes (Act CD8) and stimulatory receptor TNFRSF25 (also called DR3) and TNFRSF4 (also called OX40).And positively correlated with immature Dendritic Cells (iDC) and helper Th2 cells. Gal-8 is expressed in various tumors including breast and colorectal cancer, and is significantly associated with the progression and poor prognosis of these cancers (for correlation analysis data, see the original text).

In summary, the LGALS8 gene is expressed in various types of tumors, especially showing high/heterogeneous expression in breast and colorectal cancer, suggesting its potential value in these areas. It tends to be highly expressed in subtypes with a high tumor mutation burden, further indicating its relation to immune cell infiltration and immune factor regulation. Gal-8 is a potential therapeutic target for cancer, warranting further preclinical research and development.

Original article link：https://mp.weixin.qq.com/s/1NAlK7hzYgTWDfkblu1uOw