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Project
Deciphering the dendritic cell compartment in ovarian cancer to assess their potential as tumor vaccines. (FWOAL1009)
Advanced stage ovarian cancer (OC) patients only have an overall 5-
year survival of 20%. While targeted therapies such as PARP
inhibitors have improved progression free survival, immunotherapy
has so far not resulted in clear patient benefit. Importantly, the role of
tumor-dendritic cells (DCs) as a key player in mounting an adaptive
immune response has not been investigated yet in OC. Indeed, our
lab has uncovered that vaccination with tumor-cDCs can elicit a
therapeutically relevant immune response.
Therefore, in this project, we will evaluate the cDC heterogeneity in
OC and the potential to use tumor-cDCs as vaccine to treat OC.
More specifically, we will identify and characterize different cDC
populations at the transcriptomic, proteomic and functional level in
both a murine OC model and patient samples using state-of-the-art
technologies. As in OC, BRCA1/2 mutations are present in 20% of
the patients and determine patient outcome, their role in defining
cDC function will also be studied. On top, we will investigate the
impact of chemotherapy and PARP inhibitors on tumor-cDC function
and assess the role of immunosuppressive cells thereon. As last, in
the murine OC model, the effectiveness of the different cDC
populations as OC vaccine will be assessed.
The results of this project will provide new insights into the role of
cDCs in OC and will propose a novel therapeutic approach for OC
that overcomes the currently witnessed barriers to effective
therapeutic responses.
year survival of 20%. While targeted therapies such as PARP
inhibitors have improved progression free survival, immunotherapy
has so far not resulted in clear patient benefit. Importantly, the role of
tumor-dendritic cells (DCs) as a key player in mounting an adaptive
immune response has not been investigated yet in OC. Indeed, our
lab has uncovered that vaccination with tumor-cDCs can elicit a
therapeutically relevant immune response.
Therefore, in this project, we will evaluate the cDC heterogeneity in
OC and the potential to use tumor-cDCs as vaccine to treat OC.
More specifically, we will identify and characterize different cDC
populations at the transcriptomic, proteomic and functional level in
both a murine OC model and patient samples using state-of-the-art
technologies. As in OC, BRCA1/2 mutations are present in 20% of
the patients and determine patient outcome, their role in defining
cDC function will also be studied. On top, we will investigate the
impact of chemotherapy and PARP inhibitors on tumor-cDC function
and assess the role of immunosuppressive cells thereon. As last, in
the murine OC model, the effectiveness of the different cDC
populations as OC vaccine will be assessed.
The results of this project will provide new insights into the role of
cDCs in OC and will propose a novel therapeutic approach for OC
that overcomes the currently witnessed barriers to effective
therapeutic responses.
Date:1 Jan 2021 → Today
Keywords:Dendritic cell heterogeneity in ovarian cancer, Dendritic cell vaccines as novel therapeutic option in ovarian cancer, Resistance mechanisms in ovarian cancer
Disciplines:Adaptive immunology, Cancer therapy, Single-cell data analysis