Abstract
Background: Immunotherapy has been proposed as a treatment to stop breast cancer (BrCa) progression. However, there has been limited success in this treatment. This implies that BrCa tumors have another immune evasion mechanism(s). While the kynurenine pathway (KP) is known to be a key player in mediating tumor immune evasion and shown to have a potential role in cancer, little is known about KP involvement in BrCa.
Aims: This study aims to fully characterize the activity of the KP in each BrCa subtype and to investigate whether variations in serum KP parameters are associated with particular BrCa clinical subtype.
Methods: To understand how KP is regulated in BrCa, we examined the KP profile in BrCa cell lines (n = 7) and clinical samples (n = 1997) that represent major subtypes of BrCa (luminal, HER2-enriched, and triple-negative [TN]). We carried out qPCR, western blot/immunohistochemistry, and ultra-high pressure liquid chromatography to quantify KP enzyme gene, protein, and activity, respectively.
Results: We revealed that the KP is highly dysregulated in the HER2-enriched and TN BrCa subtype. Our multi-omics approach has shown that the KP enzymes KMO and KYNU are highly upregulated in the HER2-enriched and TN BrCa subtype, leading to the increased production of the potent immunosuppressive metabolite, 3-hydroxylanthranilic acid.
Discussion: Our data indicate that KP is dysregulated in all BrCa and may be the major facilitator in the evasion of immune surveillance in TN BrCa. Significantly, our study shows that serum KP profiles can successfully discriminate TN BrCa patients from other BrCa patients.
Translational significance: Our work will highlight the role of KP in BrCa, and potentially identify a new blood-based biomarker to identify triple-negative BrCa patients.
Aims: This study aims to fully characterize the activity of the KP in each BrCa subtype and to investigate whether variations in serum KP parameters are associated with particular BrCa clinical subtype.
Methods: To understand how KP is regulated in BrCa, we examined the KP profile in BrCa cell lines (n = 7) and clinical samples (n = 1997) that represent major subtypes of BrCa (luminal, HER2-enriched, and triple-negative [TN]). We carried out qPCR, western blot/immunohistochemistry, and ultra-high pressure liquid chromatography to quantify KP enzyme gene, protein, and activity, respectively.
Results: We revealed that the KP is highly dysregulated in the HER2-enriched and TN BrCa subtype. Our multi-omics approach has shown that the KP enzymes KMO and KYNU are highly upregulated in the HER2-enriched and TN BrCa subtype, leading to the increased production of the potent immunosuppressive metabolite, 3-hydroxylanthranilic acid.
Discussion: Our data indicate that KP is dysregulated in all BrCa and may be the major facilitator in the evasion of immune surveillance in TN BrCa. Significantly, our study shows that serum KP profiles can successfully discriminate TN BrCa patients from other BrCa patients.
Translational significance: Our work will highlight the role of KP in BrCa, and potentially identify a new blood-based biomarker to identify triple-negative BrCa patients.
| Original language | English |
|---|---|
| Pages (from-to) | 15-16 |
| Number of pages | 2 |
| Journal | Asia-Pacific Journal of Clinical Oncology |
| Volume | 17 |
| Issue number | S5 |
| Publication status | Published - Sept 2021 |
| Event | Sydney Cancer Conference 2021 - Sydney, Australia Duration: 9 Sept 2021 → 10 Sept 2021 |