V. Geldhof MD, PhD

Simply the B(r)east: Endothelial cell heterogeneity in health and disease

SUMMARY

This thesis aimed to unveil new insights into breast cancer (BC) vasculature, since this could potentially have a large clinical impact. To do so, single-cell RNA-sequencing was performed on the breast cancer vasculature and tumour microenvironment. The analysis revealed novel interactions between immune cells and endothelial cells (ECs), and identified a capillary EC subtype, called lipid processing ECs (LIPECs), expressing genes regulated by PPAR-γ. Retrospectively, this study uncovered breast cancer-specific clinical benefits of PPAR-γ agonist (metformin) treatment, positively correlated with LIPEC abundance. In conclusion, these findings unravelled heterogeneity in breast ECs, and raise the question of whether targeting specific EC subtypes is a potential avenue for BC treatment.

(Belg J Med Oncol 2023;17(3):88–90)

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Immune checkpoint inhibition in triple negative breast cancer: targeting Achilles’ heel?

Triple negative breast cancers pose an important challenge both for patients and their clinicians due to their aggressive disease course, poor long-term survival and lack of effective systemic treatment options. Recent scientific advances show that the adaptive immune system harbors the intrinsic capacity to eradicate cancer, generally through mechanisms that involve cytotoxic T-cells. Immune checkpoint inhibition boosts the host-anti-tumor response in many solid tumors, including breast cancer. However, cancer cells acquire ways to evade immunosurveillance and intra-tumoral T-cells are often functionally impaired, resulting in overt clinical cancer. Interestingly, the efficacy of immune checkpoint inhibition appears to correlate with tumor immunogenicity and the tumor mutational burden. Triple negative breast cancer has the highest tumor mutational burden of all breast cancer subtypes and therefore is believed to be the most immunogenic subtype. For this reason, clinical trials to date mainly focus on this specific subtype. Here, we review the accumulating evidence for immune checkpoint blockade in triple negative breast cancer.

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Immune checkpoint inhibition in triple negative breast cancer: targeting Achilles’ heel?

Triple negative breast cancers pose an important challenge both for patients and their clinicians due to their aggressive disease course, poor long-term survival and lack of effective systemic treatment options. Recent scientific advances show that the adaptive immune system harbors the intrinsic capacity to eradicate cancer, generally through mechanisms that involve cytotoxic T-cells. Immune checkpoint inhibition boosts the host-anti-tumor response in many solid tumors, including breast cancer. However, cancer cells acquire ways to evade immunosurveillance and intra-tumoral T-cells are often functionally impaired, resulting in overt clinical cancer. Interestingly, the efficacy of immune checkpoint inhibition appears to correlate with tumor immunogenicity and the tumor mutational burden. Triple negative breast cancer has the highest tumor mutational burden of all breast cancer subtypes and therefore is believed to be the most immunogenic subtype. For this reason, clinical trials to date mainly focus on this specific subtype. Here, we review the accumulating evidence for immune checkpoint blockade in triple negative breast cancer.

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P.04 ENDOTHELIAL CELL METABOLISM BLOCKADE TO INDUCE TUMOR VESSEL NORMALIZATION AND IMPROVE CURRENT IMMUNOTHERAPY

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