Tumor Immunotherapy Based On Bladder Cancer-Specific Infiltrating T Cells And Tim3/Lag3 Aptamer

Bladder cancer is a common malignant tumor that affects about600,000 people and kills 210,000 people each year.Immunotherapy is a new cancer treatment method,mainly targeting T cells,the situation of T cells is very complex,therefore,an urgent problem to be solved is how to deeply analyze T cells.To elucidate the status and function of infiltrating T cells in bladder cancer,we detected T cells in tumor tissues,normal tissues and PBMC of two patients with invasive bladder cancer using single-cell RNA sequencing,and screened out four tumor-specific infiltrating T cell subsets.exhausted T cells(T_Ex),exhausted natural killer T cells(NKT_Ex),Ki67⁺T cells（Ki67⁺T）,and B cell like T cell（B-T）.Further analysis showed that these subsets were negatively correlated with the prognosis of patients with tumors.In order to study the role of T_Exin tumor immunotherapy,aptamers targeting the immune checkpoint LAG3 and TIM3 that were high expressed in T_Exwere prepared.LAG3 and TIM3 aptamers could promote Jurkat cell proliferation,and the increase rate was 37.62～49.63%.The expression of cytokines in Jurkat cells increased by 27.84～207.13%after aptamer treatment.After co-incubation with tumor cells,the mortality of tumor cells increased by 183.95～231.03%,indicating that the aptamer could significantly enhance the tumor killing ability of Jurkat cells in vitro.In conclusion,T_Ex,NKT_Ex,Ki67⁺T and B-T are tumor-specific infiltrating T cell subsets,which are negatively correlated with the prognosis of bladder cancer patients.By targeting LAG3 or TIM3 that were high expressed in T_Ex,the tumor killing ability of T cells can be effectively enhanced.