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  • Mezheyeuski, ArturUppsala University,Uppsala universitet,Cancerprecisionsmedicin (author)

An immune score reflecting pro- and anti-tumoural balance of tumour microenvironment has major prognostic impact and predicts immunotherapy response in solid cancers

  • Article/chapterEnglish2023

Publisher, publication year, extent ...

  • Elsevier,2023
  • electronicrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:uu-501100
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-501100URI
  • https://doi.org/10.1016/j.ebiom.2023.104452DOI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:152375182URI
  • https://lup.lub.lu.se/record/5dafa429-dfa9-42a3-8e09-97375ac0f242URI

Supplementary language notes

  • Language:English
  • Summary in:English

Part of subdatabase

Classification

  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • Background: Cancer immunity is based on the interaction of a multitude of cells in the spatial context of the tumour tissue. Clinically relevant immune signatures are therefore anticipated to fundamentally improve the accuracy in predicting disease progression.Methods: Through a multiplex in situ analysis we evaluated 15 immune cell classes in 1481 tumour samples. Single-cell and bulk RNAseq data sets were used for functional analysis and validation of prognostic and predictive associations.Findings: By combining the prognostic information of anti-tumoural CD8+ lymphocytes and tumour supportive CD68+CD163+ macrophages in colorectal cancer we generated a signature of immune activation (SIA). The prognostic impact of SIA was independent of conventional parameters and comparable with the state-of-art immune score. The SIA was also associated with patient survival in oesophageal adenocarcinoma, bladder cancer, lung adenocarcinoma and melanoma, but not in endometrial, ovarian and squamous cell lung carcinoma. We identified CD68+CD163+ macrophages as the major producers of complement C1q, which could serve as a surrogate marker of this macrophage subset. Consequently, the RNA-based version of SIA (ratio of CD8A to C1QA) was predictive for survival in independent RNAseq data sets from these six cancer types. Finally, the CD8A/C1QA mRNA ratio was also predictive for the response to checkpoint inhibitor therapy.Interpretation: Our findings extend current concepts to procure prognostic information from the tumour immune microenvironment and provide an immune activation signature with high clinical potential in common human cancer types.

Subject headings and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Backman, Max,1987-Uppsala University,Uppsala universitet,Institutionen för immunologi, genetik och patologi(Swepub:uu)maxba655 (author)
  • Mattsson, Johanna Sofia Margareta,1985-Uppsala University,Uppsala universitet,Cancerimmunterapi(Swepub:uu)johma961 (author)
  • Martin-Bernabe, AlfonsoKarolinska Institute,Karolinska Institutet (author)
  • Larsson, Chatarina,1979-Uppsala University,Uppsala universitet,Cancerprecisionsmedicin(Swepub:uu)chlar838 (author)
  • Hrynchyk, InaCity Clin Pathologoanat Bur, Minsk 220116, BELARUS.,City Clinical Pathologoanatomic Bureau, Minsk (author)
  • Hammarström, Klara,1990-Uppsala University,Uppsala universitet,Cancerprecisionsmedicin(Swepub:uu)klaha235 (author)
  • Ström, SimonUppsala University,Uppsala universitet,Institutionen för immunologi, genetik och patologi (author)
  • Ekström, Joakim,1982-Uppsala University,Uppsala universitet,Cancerprecisionsmedicin(Swepub:uu)joaek270 (author)
  • Mauchanski, SiarheiKarolinska Institute (author)
  • Khelashvili, SalomeNN Alexandrov Natl Canc Ctr Belarus, Minsk 223040, BELARUS. (author)
  • Lindberg, AmandaUppsala universitet,Cancerimmunterapi(Swepub:uu)amali280 (author)
  • Agnarsdóttir, Margrét,1970-Uppsala universitet,Institutionen för immunologi, genetik och patologi(Swepub:uu)marag973 (author)
  • Edqvist, Per-Henrik DUppsala universitet,Cancerprecisionsmedicin(Swepub:uu)peedq227 (author)
  • Huvila, JuttaUniv Turku, Dept Pathol, Turku 20500, Finland. (author)
  • Segersten, UlrikaUppsala universitet,Urologkirurgi(Swepub:uu)ulriande (author)
  • Malmström, Per-UnoUppsala universitet,Urologkirurgi(Swepub:uu)perunoms (author)
  • Botling, JohanUppsala universitet,Cancerprecisionsmedicin(Swepub:uu)johanbot (author)
  • Nodin, BjörnLund University,Lunds universitet,Terapeutisk patologi,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Therapeutic pathology,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,LUCC: Lund University Cancer Centre,Other Strong Research Environments(Swepub:lu)immu-bnn (author)
  • Hedner, CharlottaLund University,Lunds universitet,Terapeutisk patologi,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Therapeutic pathology,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,LUCC: Lund University Cancer Centre,Other Strong Research Environments(Swepub:lu)med-cah (author)
  • Borg, DavidLund University,Lunds universitet,Terapeutisk patologi,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Therapeutic pathology,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,LUCC: Lund University Cancer Centre,Other Strong Research Environments(Swepub:lu)onk-dbo (author)
  • Brändstedt, JennyLund University,Lunds universitet,Kirurgi,Forskargrupper vid Lunds universitet,Surgery,Lund University Research Groups(Swepub:lu)med-jyb (author)
  • Sartor, HannaLund University,Lunds universitet,Diagnostisk radiologi, Malmö,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Radiology Diagnostics, Malmö,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Skåne University Hospital(Swepub:lu)med-hso (author)
  • Leandersson, KarinLund University,Lunds universitet,Cancerimmunologi, Malmö,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Cancer Immunology, Malmö,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments(Swepub:lu)immu-kpe (author)
  • Glimelius, BengtUppsala universitet,Cancerprecisionsmedicin(Swepub:uu)bengglim (author)
  • Portyanko, AnnaNN Alexandrov Natl Canc Ctr Belarus, Minsk 223040, BELARUS. (author)
  • Pontén, FredrikUppsala University,Uppsala universitet,Cancerprecisionsmedicin(Swepub:lu)tbio-fip (author)
  • Jirström, KarinLund University,Lunds universitet,Terapeutisk patologi,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Therapeutic pathology,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,LUCC: Lund University Cancer Centre,Other Strong Research Environments(Swepub:lu)pat-kji (author)
  • Micke, PatrickUppsala universitet,Cancerimmunterapi(Swepub:uu)patmi676 (author)
  • Sjöblom, TobiasUppsala universitet,Cancerprecisionsmedicin(Swepub:uu)tobisjob (author)
  • Uppsala universitetCancerprecisionsmedicin (creator_code:org_t)

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  • In:EBioMedicine: Elsevier882352-3964

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