Comparative evaluation of T-cell receptors in experimental glioma-draining lymph nodes. Issue 1 (28th September 2021)

• Record Type: Journal Article
• Authors: Blobner, Jens; Kilian, Michael; Tan, Chin Leng; Aslan, Katrin; Sanghvi, Khwab; Meyer, Jochen; Fischer, Manuel; Jähne, Kristine; Breckwoldt, Michael O; Sahm, Felix; von Deimling, Andreas; Bendszus, Martin; Wick, Wolfgang; Platten, Michael; Green, Edward; Bunse, Lukas
• Is Part Of: Neuro-oncology advances. Volume 3:Issue 1(2021)
• Publication Date: 2021-09-28
• Subjects: glioma draining lymph nodes -- glioblastoma -- TCR discovery; 616.99481
• DOI: 10.1093/noajnl/vdab147
• Languages: English
• ISSNs: 2632-2498

Abstract

Abstract: Background: Glioblastomas, the most common primary malignant brain tumors, are considered immunologically cold malignancies due to growth in an immune sanctuary site. While peptide vaccines have shown to generate intra-tumoral antigen-specific T cells, the identification of these tumor-specific T cells is challenging and requires detailed analyses of tumor tissue. Several studies have shown that CNS antigens may be transported via lymphatic drainage to cervical lymph nodes, where antigen-specific T-cell responses can be generated. Therefore, we investigated whether glioma-draining lymph nodes (TDLN) may constitute a reservoir of tumor-reactive T cells. Methods: We addressed our hypothesis by flow cytometric analyses of chicken ovalbumin (OVA)-specific CD8 + T cells as well as T-cell receptor beta (TCRβ) next-generation-sequencing (TCRβ-NGS) of T cells from tumor tissue, TDLN, spleen, and inguinal lymph nodes harvested from experimental mouse GL261 glioma models. Results: Longitudinal dextramer-based assessment of specific CD8 + T cells from TDLN did not show tumor model antigen reactivity. Unbiased immunogenomic analysis revealed a low overlap of TCRβ sequences from glioma-infiltrating CD8 + T cells between mice. Enrichment scores, calculated by the ratio of productive frequencies of the different TCRβ-CDR3 amino-acid (aa) rearrangements of CD8 + T cells derived from tumor, TDLN, inguinal lymph nodes, and spleen demonstrated a higher proportion of tumor-associated TCR in the spleen compared to TDLN. Conclusions: In experimental glioblastoma, our data did not provide evidence that glioma-draining cervical lymph nodes are a robust reservoir for spontaneous glioma-specific T cells highlighting the requirement for detailed analyses of glioma-infiltrating T cells for the discovery of tumor-specific TCR.