Detection And Its Clinical Significance Of The Phenotypes Of Infiltrating T Cells In The Tumor Microenvironment Of Pancreatic Cancer

Objectives:To detect the phenotype of infiltrating T cells in the tumor microenvironment of pancreatic cancer and explore its clinical significance.Methods:The phenotypes of infiltrating T cells in pancreatic cancer tissue microarrays(including 60 pairs of pancreatic cancer tissues and corresponding adjacent normal tissues and 30 cases of cancer tissue alone)were detected by multiplex fluorescence immunohistochemistry.The following cell markers were used for detection,total T cells(CD3~+),CD4~+Th(CD3~++CD4~+),CD8~+CTL(CD3~++CD8~+),Tregs(CD3~++CD4~++Foxp3~+),PD-1~+T cells(CD3~++PD-1~+)and PD-L1~+T cells(CD3~++PD-L1~+).The expression differences of tumor infiltrating T cells(TILs)in pancreatic cancer tissues and adjacent normal tissues were analyzed,and its relationship with clinicopathological characteristics and postoperation survival time were analyzed.Results:1.57 pairs of pancreatic cancer tissues and corresponding adjacent normal tissues and another 25 cases of pancreatic cancer tissues were successfully detected.Compared with adjacent normal tissues,the proportion of total T cells,CD4~+Th and CD8~+CTL cells in pancreatic cancer tissues were significantly reduced(P<0.05),while the proportion of Tregs and PD-L1~+T cells were significantly increased(P<0.05).There was no significant difference in the proportion of PD-1~+T cells between pancreatic cancer tissues and adjacent normal tissues(P>0.05).Compared with adjacent normal tissues,the proportion of CD8~+CTL in total T cells in pancreatic cancer tissues was significantly reduced(P<0.05),while the proportions of Tregs and PD-L1~+T cells in total T cells were significantly increased(P<0.05).There was no significant difference in the proportion of CD4~+Th and PD-1~+T cells in total T cells between pancreatic cancer tissues and adjacent normal tissues(P>0.05).2.Patients were stratified into low or high-infiltration groups based upon the median percentages for each T-cell subpopulation.The infiltration levels of total T cells in the tumor microenvironment of pancreatic cancer was significantly correlated with tumor differentiation and T stage(P<0.05),while it was not correlated with age,gender,tumor location,tumor diameter,N stage and TNM stage(P>0.05).The infiltration levels of CD4~+Th was significantly correlated with tumor differentiation(P<0.05),while it was not correlated with age,gender,tumor location,tumor diameter,T stage,N stage and TNM stage(P>0.05).The infiltration levels of CD8~+CTL was significantly correlated with tumor differentiation(P<0.05),while it was not correlated with age,gender,tumor location,tumor diameter,T stage,N stage and TNM stage(P>0.05).The infiltration levels of Tregs was significantly correlated with N stage and TNM stage(P<0.05),while it was not correlated with age,gender,tumor location,tumor diameter,tumor differentiation and T stage(P>0.05).The infiltration levels of PD-1~+T cells was significantly correlated with tumor differentiation and T stage(P<0.05),while it was not correlated with age,gender,tumor location,tumor diameter,N stage and TNM stage(P>0.05).The infiltration levels of PD-L1~+T cells was significantly correlated with N stage and TNM stage(P<0.05),while it was not correlated with age,gender,tumor location,tumor diameter,tumor differentiation and T stage(P>0.05).3.The postoperation survival time of patients with high infiltration of total T cell,CD4~+Th and CD8~+CTL was significantly longer than that of patients with the low infiltration(P<0.05).The postoperation survival time of patients with low infiltration of Tregs and PD-L1~+T cells was significantly longer than that of patients with high infiltration(P<0.05).There was no significant difference in postoperation survival time between patients with high-infiltration and low-infiltration of PD-1~+T cells(P>0.05).Multivariate analysis showed the tumor differentiation(HR=2.733),TNM stage(HR=2.364),the infiltration levels of total T cells(HR=0.323),the infiltration levels of CD4~+Th(HR=0.393),the infiltration levels of Tregs(HR=2.786)and the infiltration levels of PD-L1~+T cells(HR=2.305)were independent risk factor for the prognosis of pancreatic cancer.Conclusions:The tumor microenvironment of pancreatic cancer has a characteristic of immunosuppressive,with the reduced immune effector cells and increased immunosuppressive cells.The phenotypes of infiltrating T cells in the tumor microenvironment are significantly associated with the prognosis of pancreatic cancer,and the infiltration levels of total T cells,CD4~+Th,Tregs and PD-L1~+T cells are independent risk factor for the prognosis of pancreatic cancer.