Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Immune profiling and identification of prognostic immune-related risk factors in human ovarian cancer
Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden..
Karolinska Univ Hosp, Dept Gynecol Oncol, Stockholm, Sweden..
Vrije Univ Amsterdam Med Ctr, Canc Ctr Amsterdam, Dept Hematol, Amsterdam, Netherlands..
Karolinska Inst, Dept Womens & Childrens Hlth, Div Obstet & Gynecol, Stockholm, Sweden..
Show others and affiliations
2019 (English)In: Oncoimmunology, ISSN 2162-4011, E-ISSN 2162-402X, Vol. 8, no 2, article id e1535730Article in journal (Refereed) Published
Abstract [en]

Suppression of immune reactivity by increased expression of co-inhibitory receptors has been discussed as a major reason as to why the immune system fails to control tumor development. Elucidating the co-inhibitory expression pattern of tumor-infiltrating lymphocytes in different cancer types will help to develop future treatment strategies. We characterized markers reflecting and affecting T-cell functionality by flow cytometry on lymphocytes isolated from blood, ascites and tumor from advanced ovarian cancer patients (n = 35). Significantly higher proportions of CD4+ and CD8+ T-cells expressed coinhibitory receptors LAG-3, PD-1 and TIM-3 in tumor and ascites compared to blood. Co-expression was predominantly observed among intratumoral CD8+ T-cells and the most common combination was PD-1 and TIM-3. Analysis of 26 soluble factors revealed highest concentrations of IP-10 and MCP-1 in both ascites and tumor. Correlating these results with clinical outcome revealed the proportion of CD8+ T-cells without expression of LAG-3, PD-1 and TIM-3 to be beneficial for overall survival. In total we identified eight immune-related risk factors associated with reduced survival. Ex vivo activation showed tumor-derived CD4+ and CD8+ T-cells to be functionally active, assessed by the production of IFN-gamma, IL-2, TNF-alpha, IL-17 and CD107a. Blocking the PD-1 receptor resulted in significantly increased release of IFN-. suggesting potential reinvigoration. The ovarian tumor environment exhibits an inflammatory milieu with abundant presence of infiltrating immune cells expressing inhibitory checkpoints. Importantly, we found subsets of CD8+ T-cells with double and triple expression of co-inhibitory receptors, supporting the need for multiple checkpoint-targeting agents to overcome T-cell dysfunction in ovarian cancer.

Place, publisher, year, edition, pages
TAYLOR & FRANCIS INC , 2019. Vol. 8, no 2, article id e1535730
Keywords [en]
Ovarian cancer, tumor-infiltrating lymphocytes, tumor-associated lymphocytes, ascites, checkpoint blockade, PD-1 blockade, co-inhibition, PD-1, TIM-3, LAG-3
National Category
Clinical Medicine
Identifiers
URN: urn:nbn:se:kth:diva-244138DOI: 10.1080/2162402X.2018.1535730ISI: 000457343600012PubMedID: 30713791Scopus ID: 2-s2.0-85057524933OAI: oai:DiVA.org:kth-244138DiVA, id: diva2:1289464
Note

QC 20190218

Available from: 2019-02-18 Created: 2019-02-18 Last updated: 2019-02-18Bibliographically approved

Open Access in DiVA

No full text in DiVA

Other links

Publisher's full textPubMedScopus

Authority records BETA

Uhlin, Michael

Search in DiVA

By author/editor
Uhlin, Michael
By organisation
Applied Physics
In the same journal
Oncoimmunology
Clinical Medicine

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 14 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf