The Expression And Clinical Pathological Significance Of PD-L1/Foxp3~+ Treg Cells In Colorectal Carcinomas Tissues

ObjectiveTo analyze the expression of PD-L1 and Foxp3~+Treg cells in colorectal cancer tissues and their relationship with the status of microsatellite instability,the basic clinicopathological features of patients and the prognosis of colorectal cancer.Whether the expression of PD-L1 and Foxp3~+Treg cells in MSI colorectal cancer is different and whether it is related to the prognosis of patients;whether PD-L1 and Foxp3~+Treg cells can be combined with MSI to be prediction index of colorectal cancer PD-1/PD-L1 immunity checkpoint inhibitor treatment;whether it can become an important factor in predicting the prognosis.To provide a certain clinical basis for the new treatment of colorectal cancer.MethodsWe collected some clinical and pathological data of 110 patients who underwent surgical resection in the 940th hospital of the People’s Liberation Army in2017.They were confirmed by the pathologist as colorectal adenocarcinoma(WHO pathological grading standard).Sometime,the 25 cases normal intestinal mucosa(near the diameter of the cancerous tissue>5 cm,no tumor cells in the pathology of the margin)was used as a control.All patients had no history of other tumors,and did not receive radiotherapy or chemotherapy before surgery.We detected the loss of expression of four mismatch repair proteins(MLH1,MSH2,MSH6,PMS2)in 110colorectal cancer tissues by immunohistochemical method.The focus was on detecting expression of PD-L1 and Foxp3 protein in cancer tissues and normal mucosa.Then we analyzed the expression of PD-L1 and Foxp3~+Treg cells in different MSI colorectal cancer patients,the relationship with clinicopathological features and prognosis,and two indicators correlation between.Finally,the distribution of PD-L1+/Foxp3+Treg cells was explored by immunohistochemical double staining.ResultsPart one1.In this group of 110 patients with colorectal cancer,41 cases belongs to dMMR,The deletion of 4 MMR proteins was based on the combined deletion of MLH1 and PMS2 expression.2.The status of MSI in colorectal cancer tissues was significantly correlated with ge-nder,location,histological type,lymph node metastasis,distant metastasis,and TNM pathological stage.The correlation was statistically significant(P<0.05).3.In colorectal cancer tissues,MSI-L patients have a poor prognosis compared with MSI-H and MSS colorectal cancer patients.Part two1.PD-L1 is expressed in colorectal cancer tissues and TILs,but is hardly expressed in normal tissues adjacent to the cancer.2.In 110 patients with colorectal cancer,the positive expression rate of PD-L1 in ca-ncer tissues was 34%(37/110),It can be seen that the expression of PD-L1 is correlated with the status of colorectal cancer MSI,and the difference has Statistical significance(P<0.05).3.The expression of PD-L1(T)in colorectal cancer tissues was different from that locations and depth of invasion,and the difference was statistically significant(P<0.05).The expression of PD-L1(I)in TILs was correlated with gender,infiltration depth and lymph node metastasis,and the difference was statistically significant(P<0.05).4.There was no significant correlation between the expression of PD-L1(T)and PFS in patients with 2 years(P=0.430).The expression of PD-L1(I)was significantly correlated with the 2-year PFS of patients,and the difference was statistically significant(P=0.042).Part three1.Foxp3 is mainly expressed in the nucleus of Treg cells of colorectal cancer,but not in cancer cells of colorectal cancer.Foxp3 expression is not observed in normal color-ectal mucosa.2.The expression of Foxp3~+Treg cells was correlated with MSI status,but the differ-ence was not statistically significant(P>0.05).3.The high infiltration were significantly correlated with depth of invasion,lymph node metastasis,distant metastasis,and pTNM staging,and the difference was statistically significant(P<0.05).4.The infiltration of Foxp3~+Treg cells was significantly correlated with the 2-year PFS of patients,and the difference was statistically significant(P<0.05).PD-L1(T)~-/Foxp3~+Treg cells Patients with high infiltration have a better prognosis than patients with other types.5.The correlation between the expression of Foxp3~+Treg cells and the expression of PD-L1(I)in cancer tissues of patients with colorectal cancer was statistically significant(P<0.05).Conclusions1.The expression of PD-L1 is correlated with the status of MSI in colorectal cancer.The prognosis of MSI-L compared with MSI-H and MSS in colorectal cancer is poor.Patients with positive expression of PD-L1 in tumor cells have a worse prognosis than patients with negative expression.2.Foxp3~+Treg cells were expressed in colorectal cancer tissues,but expression of Foxp3~+Treg cells was not observed in normal colorectal mucosa tissues.Compared with patients with low expression of Foxp3~+Treg cells,patients with high expression of Foxp3~+Treg cells had better prognosis.3.PD-L1(I)is associated with Foxp3~+Treg cells,and patients with PD-L1(T)~-/Foxp3~+Treg cells infiltration have a better prognosis.Therefore,the combination of PD-L1,Foxp3~+Treg cells and MSI can be a potential predictor of colorectal cancer PD-1/PD-L1 immunological checkpoint inhibitor therapy.