Density And Clinical Significance Of CD163+M2 Macrophages In Tumor Tissues Of Patients With Non-small Cell Lung Cancer

Background and ObjectiveLung cancer has the highest morbidity and mortality rate in the world,and more than 80%of non-small cell lung cancer patients are diagnosed with advanced stages.With the development of precision medicine research,molecular targeted therapy and immunotherapy play an increasingly important role.Targeted therapy for driver gene mutations such as EGFR,ALK positive,etc.,and those with negative driver genes but positive PD-L1 expression should use PD-1/PD-L1 inhibitors for immunotherapy,all of which have made breakthrough progress in clinical practice.However,whether it is the first-generation,second-generation,third-generation targeted drugs or immunosuppressants,resistance will inevitably occur,which is also a major challenge in clinical treatment.Exploring new predictive and prognostic biomarkers and finding new immunotherapeutic targets may become a feasible research direction to solve the current problems of chemotherapy,targeting and immune resistance.A large number of studies have shown that the polarization of TAMs to M2 macrophages is closely related to the occurrence and development of tumors and the expression of PD-L1.The molecular mechanism of M2 macrophage polarization is affected by a variety of cytokines/chemokines,miRNAs,signal transduction,tumor microenvironment metabolism,and tumor microenvironment dynamics.This study examined the distribution and number of CD163+M2 macrophages in non-small cell lung cancer tissues by immunohistochemical methods,and explored the effects of CD163+M2 macrophages density and PD-L1 expression on the prognosis of patients with non-small cell lung cancer.Materials and MethodsA total of 41 specimens of tissue wax from surgically resected non-small cell lung cancer patients in the Department of Pathology of the Second Affiliated Hospital of Zhengzhou University were selected.The control group consisted of 40 cases of normal tissue adjacent to the cancer,immunohistochemistry was used to detect CD 163 expression of M2 macrophages(tumor island M2 macrophages,stromal M2 macrophages)in cancer and normal tissues adjacent to cancer,and PD-L1 expression on tumor cells.SPSS 23.0 software was used for statistical analysis.The best cut-off value of M2 macrophage grouping was obtained by time-dependent ROC analysis.Measurement data were tested by t test.Count data were compared by ?2 test.Correlation analysis applies spearman rank correlation analysis,survival analysis used Kaplan-Meier test to compare univariate survival analysis,and COX risk model multivariate analysis to compare prognostic factors.Inspection level ?=0.05.Results1.In 41 cases of lung cancer,tumor islets CD163+M2=6.5 and stroma CD163+M2=8.5 were selected as the cut-off points for evaluation.The patients were divided into a tumor islets CD163+M2 macrophage high density group(tumor islets M2>6.5,28 cases),and tumor islets CD163+M2 macrophage was low density group(tumor islets M2<6.5,13 cases),stroma CD163+M2 macrophage high density group(stroma M2>8.5,22 cases),stroma CD163+M2 macrophage low density group(stroma M2<8.5,19 cases).Among the 40 normal tissues adjacent to cancer,the stroma CD163+M2 macrophage high density group(stromal M2>8.5,4 cases)and the stroma CD163+M2 macrophage low density group(stromal M2<8.5,36 cases),compared with high-density rate of CD163+M2 macrophages in cancer tissues and normal tissues adjacent to cancer:?2=17.706,p<0.001,the difference is statistically significant.2.There was no significant difference between the density of tumor islets CD163+M2 macrophage and the gender,age,smoking index,PD-L1,pathological grouping of lymph nodes,and pathological types,which was statistically significant with the clinical stage of patients(?2=6.850,p=0.014),statistically significant with Ki-67(?2=2.940,p=0.005),3.There was no significant correlation between the density of tumor islands CD163+M2 macrophages and the expression of PD-Ll,and no significant correlation between the density of stroma CD163+M2 macrophage and the expression of PD-L1(p>0.05),and the density of tumor islets CD163+M2 and stroma CD163+M2 were positively correlated(r=0.314,p=0.046).4.The pathological stages of lymph nodes(p=0.016),tumor islets CD163+M2 macrophage density(p=0.007),stroma CD163+M2 macrophage density(p=0.029),and PD-L1 expression(p=0.019)were all influencing factors of RFS,and the differences were statistically significant.5·Multivariate Cox regression analysis showed that pN1(p=0.001),pN2(p=0.015),PD-L1 expression(p=0.017),tumor islets CD163+M2 macrophage density(p=0.005),and stroma CD163+M2 macrophage density(p=0.009)were Independent factors affecting RFS in non-small cell lung cancer.Conclusions1.Non-small cell lung cancer tissues with high density of tumor islets CD163+M2 macrophages and stroma CD163+M2 macrophages have shorter RFS than patients with low density,PD-L1 positive expression was shorter RFS than negative patients.2.There was a significant correlation between the density of tumor island CD163+M2 macrophage and the density of stromal CD163+M2 macrophage in non-small cell lung cancer tissues,and there was no correlation between the two and PD-L1 expression.The density of tumor islets CD163+M2 macrophages is related to the clinical stage of patients and Ki-67,and has no correlation with gender,age,smoking index,PD-L1,pathological grouping of lymph nodes,and pathological types;stroma CD163+M2 macrophages density were not associated with clinical features of the appeal.3.pN1,pN2,PD-L1,tumor islets CD163+M2 macrophages density,and stroma CD163+M2 macrophages density were independent risk factors for RFS in non-small cell lung cancer.