High-dimensional and single-cell transcriptome analysis of the tumor microenvironment in angioimmunoblastic T cell lymphoma (AITL)

Angioimmunoblastic T-cell lymphoma (AITL) is an aggressive lymphoid malignancy associated with a poor clinical prognosis. The AITL tumor microenvironment (TME) is unique, featuring a minority population of malignant CD4+ T follicular helper (TFH) cells inter-mixed with a diverse infiltrate of multi-lineage immune cells. While much of the understanding of AITL biology to date has focused on characteristics of the malignant clone, less is known about the many non-malignant populations that comprise the TME. Recently, mutational consistencies have been identified between malignant cells and non-malignant B cells within the AITL TME. As a result, a significant role for non-malignant populations in AITL biology has been increasingly hypothesized. In this study, we have utilized mass cytometry and single-cell transcriptome analysis to identify several expanded populations within the AITL TME. Notably, we find that B cells within the AITL TME feature decreased expression of key markers including CD73 and CXCR5. Furthermore, we describe the expansion of distinct CD8+ T cell populations that feature an exhausted phenotype and an underlying expression profile indicative of dysfunction, impaired cytotoxicity, and upregulation of the chemokines XCL2 and XCL1.

Automated summary

AITL is an aggressive lymphoid malignancy with a unique tumor microenvironment characterized by a minority population of malignant TFH cells and a diverse infiltrate of immune cells. Non-malignant populations within the TME, such as B cells and CD8+ T cells, are increasingly recognized for their potential role in AITL biology. These non-malignant populations exhibit specific expression patterns that may contribute to the understanding of AITL pathogenesis.