Postdoctoral scholar Washington University in Saint Louis Saint Louis, Missouri, United States
Disclosure(s):
Muddassar Hameed, PhD: No financial relationships to disclose
Introduction/Rationale: Tumor-infiltrating γδ T cells play heterogeneous roles in cancer development and progression. However, it is unclear how the tumor microenvironment shapes γδ T heterogeneity which affects their functional roles in triple negative breast cancer (TNBC).
Methods: We performed scRNA-seq from mouse E0771 derived γδ T cells and revealed that TNBC tumor microenvironment (TME) leads to the development of distinct subsets of γδ T cells during tumor development and progression. Furthermore, we validated this observation in vivo in the E0771 TNBC mouse model.
Results: We observed that γδ T cells have unique transcriptional homogeneous naïve, effector, exhausted, and senescent γδ T cell populations. Different functional states of γδ T cells showed distinct metabolic and transcriptional profiles, which significantly link to their functional role in anti-tumor activity. Furthermore, clinical data from TNBC patients shows that human γδ T also express high levels of exhaustion and senescent markers which have positive correlation with worst disease progression in patients.
Conclusion: This study provides a comprehensive landscape of γδ T cells in the TNBC TME, revealing their heterogeneity and potential role in disease development.
