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

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Changes in the Tumor Immune Microenvironment during Disease Progression in Patients with Ovarian Cancer. / Westergaard, Marie Christine Wulff; Milne, Katy; Pedersen, Magnus; Hasselager, Thomas; Olsen, Lars Rønn; Anglesio, Michael S; Borch, Troels Holz; Kennedy, Mia; Briggs, Gillian; Ledoux, Stacey; Kreuzinger, Caroline; Decken, Isabel von der; Donia, Marco; Castillo-Tong, Dan Cacsire; Nelson, Brad H; Svane, Inge Marie.

In: Cancers, Vol. 12, No. 12, 3828, 2020.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Westergaard, MCW, Milne, K, Pedersen, M, Hasselager, T, Olsen, LR, Anglesio, MS, Borch, TH, Kennedy, M, Briggs, G, Ledoux, S, Kreuzinger, C, Decken, IVD, Donia, M, Castillo-Tong, DC, Nelson, BH & Svane, IM 2020, 'Changes in the Tumor Immune Microenvironment during Disease Progression in Patients with Ovarian Cancer', Cancers, vol. 12, no. 12, 3828. https://doi.org/10.3390/cancers12123828

APA

Westergaard, M. C. W., Milne, K., Pedersen, M., Hasselager, T., Olsen, L. R., Anglesio, M. S., Borch, T. H., Kennedy, M., Briggs, G., Ledoux, S., Kreuzinger, C., Decken, I. V. D., Donia, M., Castillo-Tong, D. C., Nelson, B. H., & Svane, I. M. (2020). Changes in the Tumor Immune Microenvironment during Disease Progression in Patients with Ovarian Cancer. Cancers, 12(12), [3828]. https://doi.org/10.3390/cancers12123828

Vancouver

Westergaard MCW, Milne K, Pedersen M, Hasselager T, Olsen LR, Anglesio MS et al. Changes in the Tumor Immune Microenvironment during Disease Progression in Patients with Ovarian Cancer. Cancers. 2020;12(12). 3828. https://doi.org/10.3390/cancers12123828

Author

Westergaard, Marie Christine Wulff ; Milne, Katy ; Pedersen, Magnus ; Hasselager, Thomas ; Olsen, Lars Rønn ; Anglesio, Michael S ; Borch, Troels Holz ; Kennedy, Mia ; Briggs, Gillian ; Ledoux, Stacey ; Kreuzinger, Caroline ; Decken, Isabel von der ; Donia, Marco ; Castillo-Tong, Dan Cacsire ; Nelson, Brad H ; Svane, Inge Marie. / Changes in the Tumor Immune Microenvironment during Disease Progression in Patients with Ovarian Cancer. In: Cancers. 2020 ; Vol. 12, No. 12.

Bibtex

@article{f0048057156343349576eb6a24557f43,
title = "Changes in the Tumor Immune Microenvironment during Disease Progression in Patients with Ovarian Cancer",
abstract = "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.",
author = "Westergaard, {Marie Christine Wulff} and Katy Milne and Magnus Pedersen and Thomas Hasselager and Olsen, {Lars R{\o}nn} and Anglesio, {Michael S} and Borch, {Troels Holz} and Mia Kennedy and Gillian Briggs and Stacey Ledoux and Caroline Kreuzinger and Decken, {Isabel von der} and Marco Donia and Castillo-Tong, {Dan Cacsire} and Nelson, {Brad H} and Svane, {Inge Marie}",
year = "2020",
doi = "10.3390/cancers12123828",
language = "English",
volume = "12",
journal = "Cancers",
issn = "2072-6694",
publisher = "M D P I AG",
number = "12",

}

RIS

TY - JOUR

T1 - Changes in the Tumor Immune Microenvironment during Disease Progression in Patients with Ovarian Cancer

AU - Westergaard, Marie Christine Wulff

AU - Milne, Katy

AU - Pedersen, Magnus

AU - Hasselager, Thomas

AU - Olsen, Lars Rønn

AU - Anglesio, Michael S

AU - Borch, Troels Holz

AU - Kennedy, Mia

AU - Briggs, Gillian

AU - Ledoux, Stacey

AU - Kreuzinger, Caroline

AU - Decken, Isabel von der

AU - Donia, Marco

AU - Castillo-Tong, Dan Cacsire

AU - Nelson, Brad H

AU - Svane, Inge Marie

PY - 2020

Y1 - 2020

N2 - 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.

AB - 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.

U2 - 10.3390/cancers12123828

DO - 10.3390/cancers12123828

M3 - Journal article

C2 - 33352957

VL - 12

JO - Cancers

JF - Cancers

SN - 2072-6694

IS - 12

M1 - 3828

ER -

ID: 262914536