Expression Of PD-L1,CD68,CD86 And CD204 In Esophageal Squamous Cell Carcinoma Tissue And Its Clinical Significance

Objective Immunotherapy has become one of the anti-tumor therapies.Immune checkpoint inhibitors,mainly PD-1/PD-L1 inhibitors,have been widely used in a variety of solid tumors and have achieved good results.However,some patients have limited benefits due to drug resistance.Therefore,it is particularly important to determine more accurate predictive biomarkers for individualized immunotherapy in clinical application.Tumor-associated macrophages(TAM)are the main immune components of tumor microenvironment,promoting tumor cell proliferation,immunosuppression and angiogenesis,leading to tumor growth and metastasis.Recently,TAM is increasingly recognized as an attractive target for PD-1/PD-L1 inhibitor combination therapy.The relationship between PD-L1 and TAM expression has not been reported in domestic esophageal squamous cell carcinoma(ESCC),so the purpose of this study is to observe the expression and clinicopathological significance of PD-L1 and TAM markers CD68(panmacrophages),CD86(M1 type macrophages)and CD204(M2 type macrophages)in domestic ESCC patients,and to explore the relationship between PD-L1 expression and CD68,CD86,and CD204 expression.Methods The data of 60 patients with esophageal squamous cell carcinoma(ESCC)who underwent radical resection of esophageal cancer in Taizhou People’s Hospital from September 2015 to September 2018 were collected.Immunohistochemical(IHC)staining was used to detect the expression level of PD-L1,CD68(panmacrophages),CD86(M1 type macrophages)and CD204(M2type macrophages).SPSS 26.0 software was used for statistical analysis.Chisquare test was used to analyze the relationship between the expression of PD-L1 and TAM in ESCC tissues and the clinicopathological characteristics,as well as the correlation between the expression of PD-L1 and TAM;Mann-Whitney U test was used to compare the difference of expression of CD68,CD86 and CD204 in cancer tissues and adjacent tissues;Kaplan-Meier was used to draw survival curve for prognostic survival analysis;The prognostic factors were evaluated by single factor and multiple factor COX regression models;P<0.05,the difference was statistically significant.Results The study found that PD-L1 was expressed in both esophageal squamous cell carcinoma and adjacent tissues,but the expression rate of PD-L1 in tumor tissue was 62%(37/60),which was significantly higher than that in adjacent tissues by 17%(5/30)(P<0.001,the difference was statistically significant).The positive expression of PD-L1 in esophageal squamous cell carcinoma was not significantly correlated with gender,age,tumor location,degree of differentiation,and lymph node metastasis,while the positive expression rate of PD-L1 was higher in ESCC tissues with deep tumor invasion and late TNM stage(P<0.05,the difference was statistically significant).The expression of CD68,CD86,and CD204 in esophageal squamous cell carcinoma was significantly higher than that in adjacent tissues(P<0.001,with a statistically significant difference).The expression of CD86 in esophageal squamous cell carcinoma was not significantly correlated with gender,age,tumor location,degree of differentiation,lymph node metastasis,depth of invasion,TNM stage,vascular invasion,and neural invasion,while the expression of CD68 was significantly correlated with depth of invasion and vascular invasion(P<0.05,the difference was statistically significant),while the expression of CD204 was significantly correlated with depth of invasion,lymph node metastasis,TNM stage Neurological invasion was significantly correlated(P<0.05,the difference was statistically significant).The expression of CD68,CD204 and PDL1 in esophageal squamous cell carcinoma was positively correlated(P<0.05,the difference was statistically significant),while the expression of CD86 and PD-L1 did not show a correlation.The expression of CD86 in esophageal squamous cell carcinoma was not significantly correlated with OS in patients.However,patients with high levels of PD-L1,CD68,and CD204 expression had shorter OS and poorer prognosis(P<0.05,with statistically significant differences).In univariate analysis,the degree of differentiation,depth of invasion,lymph node metastasis,TNM stage,neural invasion,vascular invasion,and expression of PD-L1 and CD204 were significantly correlated with 3-year survival in ESCC patients(P<0.05,with statistically significant differences).Through multivariate COX analysis,it was found that only vascular infiltration was an independent prognostic factor for ESCC patients(P<0.05,with statistically significant differences).Conclusion This study found that the expression of PD-L1 in ESCC tissues was significantly higher than that in adjacent tissues,and the high expression of PD-L1 suggested that the T stage and TNM stage were later.The expression of CD68,CD86 and CD204 in ESCC was also significantly higher than that in adjacent tissues.The higher the expression of CD68,the deeper the invasion of tumor tissue,and the greater the possibility of vascular invasion;The higher the expression of CD204,the deeper the tumor invasion,the later the TNM stage,and the more likely lymph node metastasis and nerve invasion.The expression of PD-L1 is positively correlated with the expression of CD68 and CD204 in TAM,suggesting that these two factors may be related to the regulation of PD-L1,and it is worth further exploring the value of PD-L1 in the prediction of efficacy in the treatment of immune checkpoint inhibitors;This study also suggests that ESCC patients with vascular infiltration have the worst prognosis.