Expression and inhibitory effect of T cell activation inhibitor immunoglobulin variable region domain molecules in colorectal carcinomas with K-mosargioma virus gene mutation

Abstract

Objective To investigate the role of T cell activation inhibitor immunoglobulin variable region domain (VISTA) and CD8 and CD33 molecules in the colorectal cancer tissues with different mutations in K-murine sarcoma virus oncogene (KRAS) gene exons expression and mechanisms of inhibition of VISTA and programmed cell death protein (PD1) antagonists CA170 treatment on mouse CT26 colon cancer models. Methods A total of 193 cases of colorectal cancers with pathological diagnosis and KRAS gene sequencing were collected. Immunohistochemistry was used to detect the expression of the above molecules in tumor tissues. The BALB/c mouse tumor model was constructed using the mouse colorectal cancer cell line CT26. The expression of multiple cytokines in the two groups of mouse models and changes of immune cells in the tumor and tumor volume were detected by liquid-phase protein analysis, flow cytometry and vernier caliper, respectively. The results were statistically analyzed. Results There was significant difference in the expression of VISTA, CD33 and CD8 in colorectal cancer tissues between the KRAS mutation group and the wild group (P values of 0.020, 0.001, and 0.033 respectively). The tumor volume in CA170 and control groups was (1 173.3±531.2), (6 399.4±1 790.5) mm3. The difference in tumor inhibition rate between the two groups was statistically significant (P=0.000). There were statistically significant differences in the infiltration of regulatory cells (Tregs), myeloid-derived suppressor cells (MDSCs), tumor-infiltrating lymphocytes (TIL) and the expression of cytokines granulocyte macrophage-colony stimulating factor (GM-CSF), vascular endothelial growth factor (VEGF), MCSF, chemokine 2 (CCL2), interferon (IFN)-γ, interleukin (IL)-10, IL-12 between experimental groups (P=0.010, 0.001, 0.000). Conclusion The high expression of VISTA and CD33 molecules and the low infiltration of CD8+ T cells correlate with KRAS genotyping of colorectal cancer. VISTA and PD1 antagonists CA170 treatment can improve the systemic immune status of colon cancer mice and significantly slow down the growth of colorectal cancer. Key words: Colorectal cancer; T cell activation inhibitor immunoglobulin variable region domain molecules; CD33; CD8; K-murine sarcoma virus oncogene