The First Department of Digestive Endoscopy, The Fourth Affiliated Hospital of China Medical UniversityDepartment of Health Care, Jinan Municipal Hospital of Traditional Chinese MedicineDepartment of Oncology, Zoucheng People's HospitalWard of TCM Anorectal Surgery, Feicheng Hospital Affiliated to Shandong First Medical UniversityDepartment of Oncology, Shandong Chengwu County People's Hospital
Background and Aim Methods Results Conclusion CD155/T‐cell immunoglobulin and ITIM domain suppressed anti‐cancer immunity in several cancers, but its roles in colorectal cancer were not clear. Here, we investigated its roles in CRC.The percentages of CD8+ T cells expressing TIGIT and secreting cytokines were evaluated by flow cytometry. The expression level of CD155 was determined by western blot and immunohistochemistry. The levels of cytokines were determined by enzyme‐linked immunosorbent ...更多
Background and Aim Methods Results Conclusion CD155/T‐cell immunoglobulin and ITIM domain suppressed anti‐cancer immunity in several cancers, but its roles in colorectal cancer were not clear. Here, we investigated its roles in CRC.The percentages of CD8+ T cells expressing TIGIT and secreting cytokines were evaluated by flow cytometry. The expression level of CD155 was determined by western blot and immunohistochemistry. The levels of cytokines were determined by enzyme‐linked immunosorbent assay. The activation of the nuclear factor‐kappa B pathway was examined by western blot and immunofluorescent assay.T‐cell immunoglobulin and ITIM domain was overexpressed on CD8+ T cells of CRC patients and mice. CD155 was overexpressed in mice CRC tissues and cells. The addition of CD155 recombinant protein could decrease the percentages of CD8+ T cells secreting cytokines. Blocking TIGIT could increase the percentages of cytokine‐secreting CD8+ T cells. Coculturing with CD155‐knockdown CRC cells could upregulate the percentages of CD8+ T cells secreting cytokines. Blocking TIGIT partially counteracted the effect of the knockdown of CD155. Besides, coculturing with CD155‐knockdown CRC cells could promote the secretion of cytokines, activate the NF‐κB pathway, and enhance the nuclear translocation of p65. And these effects were counteracted by the application of an NF‐κB inhibitor. Finally, blocking TIGIT played anti‐cancer roles such as suppression of tumor growth, increasing the percentages of cytokine‐secreting CD8+ T cells and activation of the NF‐κB signaling pathway.Suppressing CD155/TIGIT exerted anti‐cancer effects against CRC, and our findings provided a potential therapeutic approach to treat CRC.收起
