| Objective:Diffuse large B-cell lymphoma(DLBCL)is the most common non-Hodgkin’s lymphoma and has a high degree of heterogeneity in clinical manifestations,biological behaviors,etc.After treatment with the standard RCHOP regimen,30-50% of patients eventually relapse or progress.In recent years,immunotherapy has received extensive attention.In addition to PD-1,CTLA-4,there are many immune regulatory mechanism in the body,finely regulating the body’s anti-tumor immune response.The CD73/A2 a R adenosine immunosuppression axis is a novel immune escape mechanism discovered in recent years.The tumor releases nucleotides under hypoxic conditions.Nucleotides are hydrolyzed to adenosine by a series of enzymes.Among them,CD73 is one of the key hydrolases.Free adenosine binds to A2 a R on the surface of immune cells and exerts a series of immunosuppressive effects.CD73 is highly expressed in various solid tumors,but its prognostic value is still controversial.The expression of A2 a R in tumors is less studied.The purpose of this study was to investigate the expression of CD73 on tumor cells and A2 a R on TIL in DLBCL and its relationship with clinicopathological features and prognosis.And we further analyzed the predictive value of CD73 on tumor cells combined with CD8~+TIL in the prognosis of DLBCL patients.The study aimed to provide a theoretical basis for further study of tumor immune escape mechanism and immunotherapy in DLBCL.Methods:1.The expression of CD73 on PAX-5~+ tumor cells and A2 a R on TIL was detected by multiple immunohistochemistry and its correlation with clinicopathological features and prognosis was analyzed.2.Spearman was used to test the correlation between PAX-5~+CD73~+ and A2 a R~+TIL,and the patients were divided into four groups according to the expression of CD73 on PAX-5~+ tumor cells and A2 a R on TIL,and their correlation with prognosis was analyzed.3.Patients were divided into four groups based on the expression of CD73 on PAX-5~+ tumor cells and A2 a R on TIL,and their correlation with patient’s prognosis was further analyzed.Results:1.Of the 65 patients with DLBCL,34 were PAX-5~+CD73~+,accounting for 52.3%,31 were negative,accounting for 47.7%.PAX-5~+CD73~+ was associated with IPI,LDH,and Ki-67(P<0.05).PAX-5~+CD73~+ patients had a poorer OS than those negative,P = 0.027.2.Of the 65 patients with DLBCL,28 were A2 a R~+TIL,accounting for 43.1%,and 37 were negative,accounting for 56.9%.A2 a R~+TIL was associated with B symptoms,clinical staging,IPI,and Ki-67(P<0.05).OS was significantly worse in the A2 a R~+TIL group than in the negative group,P=0.003.3.65 patients were divided into 4 groups for survival analysis according to the expression of CD73 on PAX-5~+ tumor cells and CD8~+TIL degree of infiltration.PAX-5~+CD73~+ and CD8~+TIL low infiltration group had worse prognosis than that PAX-5~+CD73-and CD8~+TIL low infiltration group,P=0.002.4.There was a significant correlation between PAX-5~+CD73~+ and A2 a R~+TIL,r=0.339,P=0.006.5.65 patients were divided into 4 groups for survival analysis according to the expression of CD73 on PAX-5~+ tumor cells and A2 a R on TIL.PAX-5~+CD73~+ and A2 a R~+TIL group had the worst prognosis,and PAX-5~+CD73-and A2 a R-TIL group had the best prognosis,P=0.017.Conclusion:The study found that the expression of CD73 on tumor cells and A2 a R on TIL in DLBCL was associated with poor prognosis.CD73 expression on tumor cells was significantly associated with A2 a R~+TIL,and CD73 expression on tumor cells combined with A2 a R~+TIL can better stratify the prognosis of patients,among whom PAX-5~+CD73~+ and A2 a R~+TIL patients had the worst prognosis.CD73 changed the effect of CD8~+TIL on the prognosis of DLBCL patients,the prognosis of PAX-5~+CD73~+ /CD8~+ TIL low infiltration patients is worse than that of PAX-5~+CD73-/CD8~+ TIL low infiltration patients. |
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