The relationship between immune cell infiltration density in tumor parenchyma and stroma and postoperative prognosis of gastric cancer

ZHU Wen; LI Xiaoqin; TAO Qing; SHEN Ronwei; XU Min; ZHANG Wei; WANG Deqiang

doi:10.3969/j.issn.1009-0460.2025.11.007

Abstract：Objective To investigate the relationship between immune cell infiltration density in tumor parenchyma and stroma and postoperative prognosis of gastric cancer.Methods Forty-seven eligible samples were screened from the gastric cancer omics cohort of the Affiliated Hospital of Jiangsu University from January 1,2016 to December 31,2018.Multiple immunofluorescence staining was performed to detect immune cells,including CD8+T cells,M1 and M2 macrophages,natural killer(NK)cell CD56bright and CD56dim subgroups.The infiltrated cell density was calculated as the number of cells per square millimeter(cells/mm2)in tumor parenchyma and stroma,respectively.The relationship of cell density with overall survival(OS)of patients after surgery was analyzed.The infiltrated cell density along with clinical pathological features were incorporated into the least absolute shrinkage and selection operator(LASSO)Cox regression model.The optimal variables for prognostic model were selected to calculate the risk score.Results The median density(number of cells/mm2)of various immune infiltrating cells in tumor tissue was as follows:CD8+T cells 75,M1 macrophage 35,M2 macrophage 118,CD56bright NK cells 64;CD56dim NK cells 670.The median density(number of cells/mm2)of various immune infiltrating cells in tumor stroma was as follows:CD8+T cells 152,M1 macrophage 96,M2 macrophage 109,CD56bright NK cells 12,CD56dim NK cells 30.The density of 5 types of cells were divided into high(≥median)and low(<median)groups based on their median values.In the tumor parenchyma,the proportion of CD8+T cells with a high density in males was significantly lower than that in females(P=0.039),the proportion of M1 macrophages with a high density in poorly differentiated tumors was significantly lower than that in well/moderately differentiated tumors(P=0.039),and the proportion of M2 macrophages with a high density in stage Ⅲ tumors was significantly higher than that in stage Ⅰ/Ⅱ tumors(P=0.018).In the tumor stroma,the proportion of M1 macrophages with a high-density in poorly differentiated tumors was higher than that in moderately differentiated tumors(P=0.039).In the tumor parenchyma,high-density CD56dim NK cell infiltration significantly prolonged OS compared to low-density individuals(P=0.001),with a median OS of not yet reached(NR)compared to 22.0 months(95%CI:7.62-36.38).The OS of high-density macrophage M1 infiltration was significantly prolonged compared to low-density individuals(P=0.007),with a median OS of NR compared to 21.0 months(95%CI:8.48-33.52).In the tumor stroma,the OS of high-density macrophage M1 infiltration was significantly prolonged compared to low-density individuals(P=0.005),with a median OS of NR compared to 21.0 months(95%CI:14.74-27.26).The postoperative pathological staging,CD56dim NK cell infiltration degree in tumor parenchyma,M1 macrophage infiltration degree in tumor parenchyma,and M1 macrophage infiltration degree in tumor stroma were screened by the LASSO regression as variables for the prognostic model,and risk scores were calculated.According to the median risk score,patients were divided into high-risk(≥median)and low-risk(<median)groups.The OS of the high-risk group was significantly lower than that of the low-risk group(P<0.001),with a median OS of 21.0 months(95%CI:11.40-30.60)compared to NR.Conclusion The infiltration density of immune cells in tumor parenchyma and stroma is closely associated with postoperative OS of gastric cancer and can serve as prognostic biomarkers.