LINC00892 Is an lncRNA Induced by T Cell Activation and Expressed by Follicular Lymphoma-Resident T Helper Cells

Ingram Iaccarino; Fatme Mourtada; Sarah Reinke; Paurnima Patil; Gero Doose; Gianni Monaco; Steve Hoffmann; Reiner Siebert; Wolfram Klapper

doi:10.3390/ncrna8030040

LINC00892 Is an lncRNA Induced by T Cell Activation and Expressed by Follicular Lymphoma-Resident T Helper Cells

Noncoding RNA. 2022 Jun 1;8(3):40. doi: 10.3390/ncrna8030040.

Authors

Ingram Iaccarino^{1

2}, Fatme Mourtada¹, Sarah Reinke¹, Paurnima Patil³, Gero Doose⁴, Gianni Monaco⁵, Steve Hoffmann⁶, Reiner Siebert³, Wolfram Klapper¹

Affiliations

¹ Department of Pathology, Hematopathology Section and Lymph Node Registry, University of Kiel, 24105 Kiel, Germany.
² Institute of Genetics and Biophysics "A. Buzzati-Traverso", Consiglio Nazionale delle Ricerche, 80131 Naples, Italy.
³ Institute of Human Genetics, Ulm University, Ulm University Medical Center, 89081 Ulm, Germany.
⁴ ecSeq Bioinformatics GmbH, 04103 Leipzig, Germany.
⁵ Institute for Transfusion Medicine and Gene Therapy, Medical Center-University of Freiburg, 79106 Freiburg, Germany.
⁶ Leibniz Institute on Aging-Fritz Lipmann Institute (FLI), 07745 Jena, Germany.

Abstract

Successful immunotherapy in both solid tumors and in hematological malignancies relies on the ability of T lymphocytes to infiltrate the cancer tissue and mount an immune response against the tumor. Biomarkers able to discern the amount and the types of T lymphocytes infiltrating a given tumor therefore have high diagnostic and prognostic value. Given that lncRNAs are known to have a highly cell-type-specific expression pattern, we searched for lncRNAs specifically expressed by activated T cells and at the same time in a kind of lymphoma, follicular lymphoma, where the microenvironment is known to play a critical role in the regulation of antitumor immunity. We focused on a non-coding transcript, annotated as LINC00892, which reaches extremely high expression levels following cell activation in Jurkat cells. Interestingly LINC00892 has an expression pattern resembling that of genes involved in T cell memory. Accordingly, LINC00892 is mostly expressed by the effector memory and helper CD4+ T cell sub-types but not by naïve T cells. In situ analyses of LINC00892 expression in normal lymph nodes and in follicular lymphoma biopsies show that its expression is limited to CD4+ PD1^hi T cells, with a subcellular localization within the germinal center matching that of follicular helper T cells. Our analysis therefore suggests that the previously uncharacterized lncRNA LINC00892 could be a useful biomarker for the detection of CD4+ memory T cells in both normal and tumor tissues.

Keywords: Follicular Lymphoma; LINC00892; PD1; T cell activation; T helper cells; lncRNA.

Grants and funding

We are grateful to the Kinderkrebsinitiative Buchholz, HolmSeppensen (KKI), for its financial support. The work of P.P. and R.S. on epigenetic alterations in T-PLL and related disorders including lncRNA alterations is funded by DFG via SFB1074 (project B9). The Seed Funding initiative of the medical faculty of the University of Kiel is also acknowledged for its financial support to I.I.