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Rigshospitalet - en del af Københavns Universitetshospital
Udgivet

Changes in the Tumor Immune Microenvironment during Disease Progression in Patients with Ovarian Cancer

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

DOI

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  • Marie Christine Wulff Westergaard
  • Katy Milne
  • Magnus Pedersen
  • Thomas Hasselager
  • Lars Rønn Olsen
  • Michael S Anglesio
  • Troels Holz Borch
  • Mia Kennedy
  • Gillian Briggs
  • Stacey Ledoux
  • Caroline Kreuzinger
  • Isabel von der Decken
  • Marco Donia
  • Dan Cacsire Castillo-Tong
  • Brad H Nelson
  • Inge Marie Svane
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Anti-PD1/PDL1 therapy has proven efficacious against many cancers but only reached modest objective response rates against recurrent ovarian cancer. A deeper understanding of the tumor microenvironment (TME) may reveal other immunosuppressive mechanisms that warrant investigation as immunotherapeutic targets for this challenging disease. Matched primary and recurrent tumors from patients with high-grade serous ovarian carcinoma (HGSC) were analyzed by multicolor immunohistochemistry/immunofluorescence for the presence of T cells, B cells, macrophages, and for the expression of immunosuppressive and HLA molecules. Cancer- and immune-related gene expression was assessed by NanoString analysis. Recurrent tumors showed increased infiltration by immune cells, displayed higher expression of PDL1, IDO, and HLA molecules, and contained more stromal tissue. NanoString analysis demonstrated increased expression of gene signatures related to chemokines and T cell functions in recurrent tumors. The ovarian tumors showed high gene expression of LAG3 and HAVCR2 (TIM3) and enhanced levels of TIGIT and CTLA4 in recurrent tumors compared to primary tumors. The majority of HGSC developed into a more inflamed phenotype during progression from primary to recurrent disease, including indications of adaptive immune resistance. This suggests that recurrent tumors may be particularly sensitive to inhibition of adaptive immune resistance mechanisms.

OriginalsprogEngelsk
TidsskriftCancers
Vol/bind12
Udgave nummer12
ISSN2072-6694
DOI
StatusUdgivet - 18 dec. 2020

ID: 61744263