Work

SLAMF8, a potential novel immune checkpoint molecule, is associated with the prognosis of colorectal cancer

Year: 2022

Type: preprint

Abstract: Recently, immune checkpoint inhibitors (ICIs) represented by programmed cell death 1(PD-1) monoclonal antibody (mAb) have revolutionized the treatment mode of malignant tumors, and have achieved long-lasting antitumor effects in a variety of solid tumors. However, this antitumor effect is limited to a small subset of specific colorectal cancer (CRC). Therefore, screening and identifying new immune checkpoint molecules are key points and hotspots in the research field of anti-tumor immunotherapy. The signaling lymphocytic activation molecule (SLAM) family is mainly expressed by and regulates the functions of immune cells. Recent studies have shown that several SLAM family members are involved in the regulation of the tumor immune microenvironment, which are promising targets for anti-tumor immunotherapy. The signaling lymphocytic activation molecule family member 8 (SLAMF8) (B-lymphocyte activator macrophage expressed/CD353) is a type I cell surface glycoprotein and clusters on chromosome 1q21. Our previous studies have shown that SLAMF8 is a potential marker for predicting the efficacy of anti-PD1 immunotherapy in gastrointestinal tumors. To further illustrate the clinical value of SLAMF8 in CRC, we retrospectively analyzed the relationship between SLAMF8 expression and prognosis of CRC patients (CRCs), the associations of the expression levels of SLAMF8 and SLAM family other members and other classical immune checkpoint molecules, using The Cancer Genome Atlas (TCGA) dataset, RNA sequencing dataset, tissue immunohistochemical staining, and systematic follow-up. In the present study, high SLAMF8 expression is associated with poor OS in CRCs. and the mRNA expression of SLAMF8 was positively correlated with the expression of multiple classical immune checkpoints (PDL1 PDL2, CTLA4, and LILRB4) and other SLAM family members. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis suggested that high SLAMF8 expression CRC tissues were significantly enriched in signaling pathways related to tumor and immune signal regulation

Source: Research Square

DOI: 10.21203/rs.3.rs-2239673/v1