Analysis of clinical characteristics of peripheral blood cytokines in patients with tumor

He Chang; Sun Shengjie; Zhao Xiao; Li Ke; Yang Zizhong; Jiao Shunchang

doi:10.3969/j.issn.1674-3245.2025.04.019

Abstract：Objective To investigate the expression heterogeneity of 12 cytokines(IL-1β、IL-1Ra、IL-4、IL-6、IL-13、IL-17、Eotaxin、IP-10、MCP-1、RANTES、G-CSF、PDGF-BB)in peripheral blood across tumor types,age groups,genders,and seasons,thereby systematically characterizing systemic immune status and providing novel insights for cancer immunotherapy.Methods This retrospective study enrolled 1,842 malignancy patients admitted to PLA General Hospital from March 2016 to July 2023,with peripheral blood cytokine profiling.The tumor types of the enrolled patients included lung cancer,liver cancer,gastric cancer,breast cancer,colorectal cancer,pancreatic cancer,ovarian cancer and esophageal cancer.There were 1,266 male patients and 576 female patients;their ages ranged from 25 to 92 years old.The seasons were divided into spring(March to May),summer(June to August),autumn(September to November),and winter(December to February).Comparative analyses evaluated cytokine expression variations across tumor types and their correlations with age,gender,and seasonal factors.Results The expressions of nine cytokines,IL-1Ra,IL-13,IL-17,Eotaxin,G-CSF,IP-10,MCP-1,PDGF-BB and RANTES,were statistically significant in the eight tumors(x2=36.17,21.75,40.02,32.19,28.67,19.08,48.75,26.62,21.37,P＜0.001).Among them,IL-1Ra was significantly underexpressed in pancreatic cancer;IL-13 is more elevated in colorectal cancer than in liver cancer;IL-17 is highly expressed in ovarian cancer and low in esophageal cancer;RANTES is highly expressed in lung cancer;MCP-1 is highly expressed in esophageal cancer;Eotaxin was highly expressed in ovarian cancer and low in lung cancer;The concentration of IP-10 in lung cancer was significantly higher than that in colorectal cancer;PDGF-BB is underexpressed in pancreatic cancer;G-CSF is upregulated in esophageal cancer and downregulated in pancreatic cancer.However,there was no significant difference in the expression of three cytokines,IL-1β,IL-4 and IL-6,in 8 tumors(P＞0.05).The expression of cytokines was also correlated with age,and IL-4 was positively correlated with age in breast cancer(r=0.306,P＜0.001).IP-10 was weakly positively correlated with age in lung cancer and colorectal cancer(r=0.127、0.294,P＜0.001).Eotaxin increased with age in lung,liver,breast and colorectal cancers(r=0.102,0.301,0.506,0.265,P＜0.05).PDGF-BB was age-dependently down-regulated in liver,gastric,breast and colorectal cancers(r=-0.284,-0.168,-0.316,-0.308,P＜0.001).The gender differences of cytokines showed that Eotaxin in male lung cancer,PDGF-BB in liver cancer,and G-CSF in gastric cancer were significantly higher than those in female(Z=-2.29,-3.98,-2.71,P＜0.05).IL-4,IL-17,Eotaxin,IP-10 in female hepatocellular carcinoma and RANTES in gastric cancer were significantly higher than those in male(Z=-2.9,-3.63,-3.39,-2.94,-2.71,P＜0.05).The seasonal characteristics of cytokines showed that the levels of IL-1β and IL-17 in lung cancer fluctuated high in summer[0.60(0.16,1.77)、20.29(13.69,57.18)]and low in winter[0.41(0.16,0.94)、16.69(12.28,31.92)],and the difference between the two was statistically significant(x2=3.10,2.98,P＜0.05).The expression of IL-1 β in liver cancer was at a trough in spring,which was statistically significant compared with that in autumn and winter(x2=-3.69,-3.20,P＜0.05),and the expression of IL-6,IL-13 and IL-1 β in gastric cancer was down-regulated in autumn,which was statistically significant compared with that in spring,summer and winter(x2=3.64,3.05,-4.36,3.91,2.02,-2.16,4.37,2.10,-4.89,P＜0.05).Conclusion The peripheral blood cytokine profile in common malignancies is affected by tumor type,age,gender,and season,with fluctuations likely related to immune status.Existing evidence links cytokine changes to tumor immunotherapy efficacy and adverse reactions.Thus,optimizing cancer immunotherapy by incorporating these immune-related cytokine changes warrants further investigation.