دورية أكاديمية
Autoreactive napsin A-specific T cells are enriched in lung tumors and inflammatory lung lesions during immune checkpoint blockade.
| العنوان: | Autoreactive napsin A-specific T cells are enriched in lung tumors and inflammatory lung lesions during immune checkpoint blockade. |
|---|---|
| المؤلفون: | Berner, Fiamma, Bomze, David, Lichtensteiger, Christa, Walter, Vincent, Niederer, Rebekka, Hasan Ali, Omar, Wyss, Nina, Bauer, Jens, Freudenmann, Lena Katharina, Marcu, Ana, Wolfschmitt, Eva-Maria, Haen, Sebastian, Gross, Thorben, Abdou, Marie-Therese, Diem, Stefan, Knöpfli, Stella, Sinnberg, Tobias, Hofmeister, Kathrin, Cheng, Hung-Wei, Toma, Marieta, Klümper, Niklas, Purde, Mette-Triin, Pop, Oltin Tiberiu, Jochum, Ann-Kristin, Pascolo, Steve, Joerger, Markus, Früh, Martin, Jochum, Wolfram, Rammensee, Hans-Georg, Läubli, Heinz, Hölzel, Michael, Neefjes, Jacques, Walz, Juliane, Flatz, Lukas |
| المصدر: | Berner, Fiamma; Bomze, David; Lichtensteiger, Christa; Walter, Vincent; Niederer, Rebekka; Hasan Ali, Omar; Wyss, Nina; Bauer, Jens; Freudenmann, Lena Katharina; Marcu, Ana; Wolfschmitt, Eva-Maria; Haen, Sebastian; Gross, Thorben; Abdou, Marie-Therese; Diem, Stefan; Knöpfli, Stella; Sinnberg, Tobias; Hofmeister, Kathrin; Cheng, Hung-Wei; Toma, Marieta; . (2022). Autoreactive napsin A-specific T cells are enriched in lung tumors and inflammatory lung lesions during immune checkpoint blockade. Science immunology, 7(75), eabn9644. American Association for the Advancement of Science 10.1126/sciimmunol.abn9644 |
| بيانات النشر: | American Association for the Advancement of Science |
| سنة النشر: | 2022 |
| المجموعة: | BORIS (Bern Open Repository and Information System, University of Bern) |
| مصطلحات موضوعية: | 610 Medicine & health |
| الوصف: | Cancer treatment with immune checkpoint blockade (ICB) often induces immune-related adverse events (irAEs). We hypothesized that proteins coexpressed in tumors and normal cells could be antigenic targets in irAEs and herein described DITAS (discovery of tumor-associated self-antigens) for their identification. DITAS computed transcriptional similarity between lung tumors and healthy lung tissue based on single-sample gene set enrichment analysis. This identified 10 lung tissue-specific genes highly expressed in the lung tumors. Computational analysis was combined with functional T cell assays and single-cell RNA sequencing of the antigen-specific T cells to validate the lung tumor self-antigens. In patients with non-small cell lung cancer (NSCLC) treated with ICB, napsin A was a self-antigen that elicited strong CD8+ T cell responses, with ICB responders harboring higher frequencies of these CD8+ T cells compared with nonresponders. Human leukocyte antigen (HLA) class I ligands derived from napsin A were present in human lung tumors and in nontumor lung tissues, and napsin A tetramers confirmed the presence of napsin A-specific CD8+ T cells in blood and tumors of patients with NSCLC. Napsin A-specific T cell clonotypes were enriched in lung tumors and ICB-induced inflammatory lung lesions and could kill immortalized HLA-matched NSCLC cells ex vivo. Single-cell RNA sequencing revealed that these T cell clonotypes expressed proinflammatory cytokines and cytotoxic markers. Thus, DITAS successfully identified self-antigens, including napsin A, that likely mediate effective antitumor T cell responses in NSCLC and may simultaneously underpin lung irAEs. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| العلاقة: | https://boris.unibe.ch/172641Test/ |
| الإتاحة: | https://doi.org/10.1126/sciimmunol.abn9644Test https://boris.unibe.ch/172641/1/sciimmunol.abn9644.pdfTest https://boris.unibe.ch/172641Test/ |
| حقوق: | info:eu-repo/semantics/restrictedAccess |
| رقم الانضمام: | edsbas.E2190F07 |
| قاعدة البيانات: | BASE |
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