ABSTRACT
Chimeric antigen receptor (CAR) T cell shows its significant therapeutic effect in part of leukemia and lymphomas, which indicates that transgenic adoptive cellular immunotherapy may be one of the breakthroughs in treatment of solid tumors and blood diseases. The functional inhibition of CAR endogenous cells in the tumor microenvironment , molecular biology function of molecules, difficulties of CAR T cells in clinical application and the solutions , how to improve the clinical efficacy and to reduce toxic side effects for future cancer immunotherapy in clinic are reviewed in this paper.
ABSTRACT
Objective To investigation the expressions of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and its receptors in non-small cell lung cancer (NSCLC) and their clinical significances.Methods The serum expression levels of TRAIL in 79 cases of NSCLC and 80 cases of normal subjects were detected by enzyme-linked immunosorbent assay (ELISA).The expressions of TRAIL-R2 and TRAIL-R4 in 42 cases of NSCLC and matched normal tissues were detected by immunohistochemistry.The relationships among TRAIL,TRAIL-R2,TRAIL-R4 and clinicopathologic features of NSCLC were analyzed.Results The expression of TRAIL in NSCLC patients was lower than that in normal human [(994.3 ±293.0)ng/ml vs.(1 141.7 ±266.1)ng/ml,t =3.29,P =0.00].The expression of TRAIL was closely correlated with clinical stage (F =2.28,P =0.00) and differentiated degree (t =5.76,P =0.00).The positive expression rate of TRAIL-R2 in NSCLC was 73.8％ (31/42),significantly lower than that in the normal tissue 100.0％ (42/42) (x2 =3.88,P =0.05).The expression of TRAIL-R2 was closely correlated with clinical stage (x2 =27.89,P=0.00) and differentiated degree (x:=9.50,P =0.00).The positive expression rate of TRAIL-R4 in NSCLC was 81.0％ (34/42),significantly higher than that in the normal tissue 50.0％ (21/42) (x2 =7.34,P =0.01).The expression of TRAIL-R4 was also closely correlated with clinical stage (x2 =17.82,P =0.00) and differentiated degree (x2 =4.47,P =0.03).There was a negative correlation between the expression of TRAIL-R2 and TRAIL-R4 in NSCLC (r =-0.67,P=0.01).Conclusion The decrease of TRAIL and TRAIL-R2 and increase of TRAIL-R4 expression may promote the occurrence and development of NSCLC,and they may provide targets for clinical treatment of NSCLC.