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Transcriptomic sign...
Transcriptomic signatures of tumors undergoing T cell attack
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- Gokuldass, Aishwarya (author)
- Copenhagen University Hospital
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- Schina, Aimilia (author)
- Danish Cancer Society,Copenhagen University Hospital
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- Lauss, Martin (author)
- Lund University,Lunds universitet,Melanoma Genomics,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments
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- Harbst, Katja (author)
- Lund University,Lunds universitet,Lunds Melanomstudiegrupp,Forskargrupper vid Lunds universitet,Melanoma Genomics,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Lund Melanoma Study Group,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments
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- Chamberlain, Christopher Aled (author)
- Copenhagen University Hospital
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- Draghi, Arianna (author)
- Copenhagen University Hospital
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- Westergaard, Marie Christine Wulff (author)
- Copenhagen University Hospital
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- Nielsen, Morten (author)
- Copenhagen University Hospital
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- Papp, Krisztian (author)
- Eötvös Loránd University
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- Sztupinszki, Zsofia (author)
- Danish Cancer Society
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- Csabai, Istvan (author)
- Eötvös Loránd University
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- Svane, Inge Marie (author)
- Copenhagen University Hospital
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- Szallasi, Zoltan (author)
- Danish Cancer Society
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- Jönsson, Göran (author)
- Lund University,Lunds universitet,Lunds Melanomstudiegrupp,Forskargrupper vid Lunds universitet,Melanoma Genomics,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Lund Melanoma Study Group,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments
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- Donia, Marco (author)
- Copenhagen University Hospital
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(creator_code:org_t)
- 2021-07-17
- 2022
- English.
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In: Cancer Immunology, Immunotherapy. - : Springer Science and Business Media LLC. - 0340-7004 .- 1432-0851. ; 71:3, s. 553-563
- Related links:
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http://dx.doi.org/10...
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Abstract
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- Background: Studying tumor cell–T cell interactions in the tumor microenvironment (TME) can elucidate tumor immune escape mechanisms and help predict responses to cancer immunotherapy. Methods: We selected 14 pairs of highly tumor-reactive tumor-infiltrating lymphocytes (TILs) and autologous short-term cultured cell lines, covering four distinct tumor types, and co-cultured TILs and tumors at sub-lethal ratios in vitro to mimic the interactions occurring in the TME. We extracted gene signatures associated with a tumor-directed T cell attack based on transcriptomic data of tumor cells. Results: An autologous T cell attack induced pronounced transcriptomic changes in the attacked tumor cells, partially independent of IFN-γ signaling. Transcriptomic changes were mostly independent of the tumor histological type and allowed identifying common gene expression changes, including a shared gene set of 55 transcripts influenced by T cell recognition (Tumors undergoing T cell attack, or TuTack, focused gene set). TuTack scores, calculated from tumor biopsies, predicted the clinical outcome after anti-PD-1/anti-PD-L1 therapy in multiple tumor histologies. Notably, the TuTack scores did not correlate to the tumor mutational burden, indicating that these two biomarkers measure distinct biological phenomena. Conclusions: The TuTack scores measure the effects on tumor cells of an anti-tumor immune response and represent a comprehensive method to identify immunologically responsive tumors. Our findings suggest that TuTack may allow patient selection in immunotherapy clinical trials and warrant its application in multimodal biomarker strategies.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Keyword
- Adaptive immune resistance
- Anti-PD-1
- Anti-PD-L1
- Immunotherapy biomarkers
- Patient selection
- Transcriptomics
Publication and Content Type
- art (subject category)
- ref (subject category)
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- By the author/editor
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Gokuldass, Aishw ...
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Schina, Aimilia
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Lauss, Martin
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Harbst, Katja
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Chamberlain, Chr ...
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Draghi, Arianna
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show more...
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Westergaard, Mar ...
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Nielsen, Morten
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Papp, Krisztian
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Sztupinszki, Zso ...
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Csabai, Istvan
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Svane, Inge Mari ...
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Szallasi, Zoltan
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Jönsson, Göran
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Donia, Marco
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
- Articles in the publication
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Cancer Immunolog ...
- By the university
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Lund University