Single-cell transcriptomic analyses provide insights into TME related with tumor-promoting in AIDS-CNS-DLBCL.

DLBCL is a common fatal disease in AIDS patients, especially involved in CNS, due to immunity dysfunction and unknown pathogenic mechanism. We analyzed scRNA-seq data from seven AIDS patients and two immunocompetent patients. Through subgroup analysis comparing the cellular composition characteristics of different CNS-DLBCL, thereby elucidating the pathogenic drivers in distinct patient populations. In AIDS related CNS-DLBCL samples, we identified a population of tumor cells with neural characteristics, designated as neuro-signature cells. These population demonstrated high-grade malignancy, characterized by upregulated glutamate receptor expression and the ability to mimic the neural niche. In terms of mechanism, we found ERK pathway activation represented a hallmark feature of this cellular subpopulation. Additionally, as for immune landscapes, AIDS-CNS-DLBCL exhibited profound immunity dysfunction, characterized by enrichment of proinflammation TAMs and enriched tumor-killing T cells with terminally exhausted phenotype, induced by neuro-signature cells.