Immunophenotypic Landscape and Prognosis-Related mRNA Signature in Diffuse Large B Cell Lymphoma

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 separated 738 DLCBL patients into two robust subtypes with distinct immune features based on 28 immune cell types. GO analysis uncovered the concordant classification of two robust significant subtypes of DLBCL. Immunity-L group, associated with poorer outcomes, was characterized by significantly lower immune cell infiltration. Immunity-H group, associated with better outcomes, was characterized by significantly higher immune cell infiltration. Further, a prognostic gene signature related immune infiltration was established by a least absolute shrinkage and selection operator (LASSO)-Cox regression model. 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 immune 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.