ABSTRACT: Diffuse large B cell lymphoma (DLBCL) exhibits a tightly complexity immune landscape. In this study, we intended to identify different immune phenotype and to examine the immune related mRNA signature for clinical characteristic, therapeutic responsiveness as well as risk stratification and survival prediction in DLBCL. We identified two immune infiltration subtypes of DLBCL patients based on 28 immune cell types. GSEA analysis uncovered the concordant classification of two robust significant subtypes of DLBCL. Considering the convenient application of the immune infiltration subtypes for prognostic prediction, we developed a risk score based on the differentially expressed genes between the Immunity-H and Immunity-L groups. By a least absolute shrinkage and selection operator (LASSO)-Cox regression model, a sixteen-gene risk signature, comprising ANTXR1, CD3D, TIMP1, FPR3, NID2, CTLA4, LPAR6, GPR183, LYZ, PTGDS, ITK, FBN1, FRMD6, PLAU, MICAL2, C1S, was established. The comprehensive results showed that the high-risk group was correlated with lower immune infiltration, more aggressive phenotypes, lower overall survival and more sensitive to lenalidomide. In contrast, a low-risk group score was associated with higher immune infiltration, less aggressive phenotypes, better overall survival and more likely to benefit from PD-1/PD-L1 inhibitors. Finally, a nomogram comprised of the risk score and IPI score was verified to more accurately predict the overall survival of DLBCL than traditional clinical prediction models. Altogether, our data demonstrate the heterogeneity of immune patterns within DLBCL and deepen our molecular understanding of this tumor entity.
