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

Area of Science:

• Oncology
• Immunology
• Neuroscience

Background:

• Diffuse large B-cell lymphoma (DLBCL) is a frequent and fatal complication in patients with acquired immunodeficiency syndrome (AIDS), often affecting the central nervous system (CNS).
• The exact pathogenic mechanisms and immune dysregulation in AIDS-related CNS-DLBCL remain largely unknown.

Purpose of the Study:

• To elucidate the pathogenic drivers and cellular composition of CNS-DLBCL in AIDS patients by analyzing single-cell RNA sequencing data.
• To compare distinct CNS-DLBCL patient populations and identify unique characteristics.

Main Methods:

• Analysis of scRNA-seq data from seven AIDS patients and two immunocompetent individuals with CNS-DLBCL.
• Subgroup analysis to compare cellular composition and identify distinct tumor cell populations.

Main Results:

• Identification of a novel tumor cell population with neural characteristics, termed 'neuro-signature cells', in AIDS-related CNS-DLBCL.
• Neuro-signature cells exhibit high-grade malignancy, upregulated glutamate receptor expression, mimic the neural niche, and show activated ERK pathway.
• AIDS-CNS-DLBCL samples display profound immune dysfunction, with enriched pro-inflammatory tumor-associated macrophages (TAMs) and terminally exhausted tumor-killing T cells induced by neuro-signature cells.

Conclusions:

• Neuro-signature cells are a key pathogenic driver in AIDS-related CNS-DLBCL, characterized by neural mimicry and ERK pathway activation.
• These tumor cells contribute to immune dysfunction by inducing pro-inflammatory TAMs and terminally exhausted T cells.
• Understanding these mechanisms is crucial for developing targeted therapies for CNS-DLBCL in AIDS patients.