Breast cancer, ovarian cancer, and coronary artery disease (CAD) have disproportionately high prevalences among Māori in Aotearoa New Zealand. Late-stage, high-grade diagnoses are prevalent among wāhine Māori cancer patients, necessitating chemotherapy as an important component of their treatment, highlighting the importance of tailored treatments for equitable outcomes. Further, inflammation plays a key role in the initiation and progression of CAD. Insight into how this disease develops and progresses in response to inflammation is critical to ensure the inequities in cardiovascular disease burden are reduced.
We aimed to generate patient-derived tumour organoids (PDOs) from breast and ovarian tumour samples from wāhine Māori, adhering to tikanga Māori, or Māori traditional protocols designed for this project. Additionally, we investigated immune cell heterogeneity in Māori pericardial fat samples, between acute and stable CAD, to understand how different cell types may be involved in the response to acute cardiac events.
We established tikanga Māori protocols through continuous reciprocal collaborations with local iwi, healthcare and research professionals. PDO models were generated using established protocols within our research group. Tumour and pericardial fat samples were collected at time of surgery and processed for downstream analyses. Samples were processed for nuclei isolation by cryosectioning and digestion, or emulsifying, before being run through 10x genomics single nuclei RNA sequencing pipelines.
Our approach integrated whakapapa (genealogy), tika (righteousness), manaakitanga (hospitality), and mana (spiritual vitality), ensuring we cultivated meaningful relationships that acknowledged the significance of Māori tissue samples and DNA as taonga (treasures), allowing culturally safe best-practices. We established PDOs with expected morphological and molecular characteristics based on their tumour sub-type. Single nuclei RNA sequencing was performed on tumour samples and pericardial fat samples. The results, along with the integration of Māori protocols in wet-lab procedures and computational analyses, will be further discussed.