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LYMPHOMA

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

Leukemia volume 36, pages 165–176 (2022)Cite this article

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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.

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Fig. 1: AITL tumor microenvironment features CD8+ expansion, global shift in B cell phenotypes.
Fig. 2: CD4+ populations in the AITL TME.
Fig. 3: Global shift in AITL B cells marked by loss of CD73, CXCR5.
Fig. 4: Expansion of distinct CD8+ T cell populations within the AITL TME.
Fig. 5: Defining the RNA transcriptome of expanded CD8+ populations in AITL.
Fig. 6: Immunoblasts and NK cell populations in AITL.

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Acknowledgements

The authors acknowledge grant funding in support of this work from the Leukemia & Lymphoma Society (LLS), the National Institutes of Health (P50 CA97274), and the Predolin Foundation.

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  1. Department of Hematology, Mayo Clinic, Rochester, MN, USA

    Joshua C. Pritchett, Zhi-Zhang Yang, Hyo Jin Kim, Jose C. Villasboas, Xinyi Tang, Shahrzad Jalali & Stephen M. Ansell

  2. Department of Health Sciences Research and Epidemiology, Mayo Clinic, Rochester, MN, USA

    James R. Cerhan

  3. Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA

    Andrew L. Feldman

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For JRC research funding provided by NanoString and BMS/Celgene. For SMA, research funding provided by Bristol Myers Squibb, ADC Therapeutics, Seattle Genetics, Regeneron, Affimed, AI Therapeutics, Trillium and Takeda. The remaining authors report nothing to disclose.

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Pritchett, J.C., Yang, ZZ., Kim, H.J. et al. High-dimensional and single-cell transcriptome analysis of the tumor microenvironment in angioimmunoblastic T cell lymphoma (AITL). Leukemia 36, 165–176 (2022). https://doi.org/10.1038/s41375-021-01321-2

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