Expression characteristics of interleukin-1 receptor 2 in colon cancer and its impact on tumor microenvironment
Objective To elucidate the expression characteristics of interleukin-1 receptor 2(IL-1R2)in the tumor microenvironment(TME)of colon cancer and explore the role of IL-1R2 in colon cancer.Methods The single-cell RNA sequencing(scRNA-seq)data of colon cancer in the gene expres-sion omnibus(GEO)database were analyzed to determine the expression distribution of IL-1R2 gene in tumor tissues.Mice were randomly divided into control group and IL-1R2 knockout(Il1r2-/-)group.Azoxymethane(AOM)and dextran sodium sulfate(DSS)were used to induce colitis-associated colon canc-er models.On day 70 after AOM/DSS,tumor tissues were collected,and the number and diameter of tumors were counted and measured.Flow cytometry was used to analyze the differences in the infiltration of various cell populations and expression of immune checkpoint molecules in the TME between Il1r2-/-mice and control mice.Independent sample t-test was used to compare the differences between the two groups.Two-way ANOVA was used to compare weight curves.Results The scRNA-seq data of CD45+immune cells from mouse colon cancer and human colon cancer showed that IL-1R2 was highly expressed in colon cancer tissues as compared with normal tissues.There was no significant difference in the number of tumors between Il1r2-/-mice and control mice(4.750±0.977 vs.7.800±1.114,t=2.005,P＞0.05),but the tumor load of Il1r2-/-mice was significantly lower than that of control group(24.170±7.483 vs.96.000±19.990,t=3.618,P＜0.01).As compared with control mice,Il1r2-/-significantly increased CD45+immune cells in TME(35.140±3.673 vs.7.076±1.929,t=6.764,P＜0.001)and CD8+T cells(26.820±1.004 vs.15.900±2.665,t=3.835,P＜0.05),the proportion of CD4+T cells showed a de-creasing trend,and the difference was not statistically significant(P＞0.05).Compared with the control group,IL-1R2 deletion resulted in programmed death 1(PD-1)+CD4+T cells(14.340±3.401 vs.24.570±2.330,t=2.482,P＜0.05),T cell immunoglobulin domain and mucin domain-containing mole-cule-3(Tim-3)+CD4+T cells(20.740±4.001 vs.41.500±4.108,t=3.620,P＜0.01),PD-1+Tim-3+CD4+T cells(7.184±2.129 vs.15.140±1.730,t=2.900,P＜0.05),while the expression of PD-1 and Tim-3 on CD8+T cells was not significantly different(P＞0.05).Conclusion IL-1R2 is highly expressed in colon cancer,and IL-1R2 deficiency can reduce the susceptibility to colitis-associated colon cancer in mice.
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