Inefficient induction of circulating TAA-specific CD8+ T-cell responses in hepatocellular carcinoma

Abstract: Background & Aims: In hepatocellular carcinoma (HCC), CD8+ T-cell responses targeting tumor-associated antigens (TAA) are considered to be beneficial. However, the molecular profile of TAA-specific CD8+ T cells in HCC is not well defined due to their low frequency.

Results: In this study, we demonstrate that TAA-specific CD8+ T-cell responses are not efficiently induced in the peripheral blood of HCC patients as supported by the following observations: First, in HCC patients, frequencies of TAA-specific CD8+ T cells were not increased compared to healthy donors (HD) or patients with liver cirrhosis. Second, a remarkable proportion of TAA-specific CD8+ T cells were naïve despite the presence of antigen within the tumor tissue. Third, antigen-experienced TAA-specific CD8+ T cells lack the characteristic transcriptional regulation of exhausted CD8+ T cells, namely EomeshiTbetdim, and express inhibitory receptors only on a minor proportion of cells. This suggests restricted antigen recognition and further supports the hypothesis of inefficient induction and activation.

Methods: By applying peptide/MHCI tetramer-based enrichment, a method of high sensitivity, we now could define the heterogeneity of circulating TAA-specific CD8+ T cells targeting glypican-3, NY-ESO-1, MAGE-A1 and MAGE-A3. We focused on therapy-naïve HCC patients of which the majority underwent transarterial chemoembolization (TACE).

Conclusion: Our analysis reveals that circulating TAA-specific CD8+ T cells targeting 4 different immunodominant epitopes are not properly induced in therapy-naïve HCC patients thereby unravelling new and unexpected insights into TAA-specific CD8+ T-cell biology in HCC. This clearly highlights severe limitations of these potentially anti-tumoral T cells that may hamper their biological and clinical relevance in HCC

Angaben zum Objekt

• Sprache: Englisch
• Umfang: Online-Ressource
• Anmerkungen: Oncotarget. - 10 (2019) , 5194-5206, ISSN: 1949-2553
• Standort: Deutsche Nationalbibliothek Frankfurt am Main

Klassifikation und Themen

• Schlagwort: Leberzirrhose

Beteiligte, Orts- und Zeitangaben

• Urheber: Tauber, Catrin ; Schultheiß, Michael ; Luca, Raffaele De ; Büttner, Nico ; Llewellyn-Lacey, Sian ; Emmerich, Florian ; Zehe, Sebastian ; Price, David A. ; Neumann-Haefelin, Christoph ; Schmitt-Graeff, Annette ; Hofmann, Maike ; Thimme, Robert
• Beteiligte Personen und Organisationen: Institut für Transfusionsmedizin und Gentherapie
• Ereignis: Veröffentlichung
• (wo): Freiburg
• (wer): Universität
• (wann): 2020

Weitere Informationen

• DOI: 10.18632/oncotarget.27146
• URN: urn:nbn:de:bsz:25-freidok-1721646
• Rechteinformation: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Letzte Aktualisierung: 25.03.2025, 13:52 MEZ