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

Joshua C. Pritchett, Zhi Zhang Yang, Hyo Jin Kim, Jose C. Villasboas, Xinyi Tang, Shahrzad Jalali, James R. Cerhan, Andrew L. Feldman, Stephen M. Ansell

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)165-176
Number of pages12
JournalLeukemia
Volume36
Issue number1
DOIs
StatePublished - Jan 2022

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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