The EACR’s ‘Highlights in Cancer Research’ is a regular summary of the most interesting and impactful recent papers in cancer research, curated by the Board of the European Association for Cancer Research (EACR).
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Goddard, E. T., Linde, M. H. et al. Cancer Cell 42(1), 119-134.E12 (2024).
doi: doi.org/10.1016/j.ccell.2023.12.011.
Summary and graphical abstract by Alexandra Boitor, EACR Scientific Officer
Summary of the findings
A long-standing issue in combating breast cancer has been disease reoccurrence years after successful treatment of the primary tumour. Single disseminated tumour cells (DTCs), that left the primary tumour during the initial stages of tumour progression and became dormant, persisting in peripheral tissues, are believed to be at the core of breast cancer recurrence.
In this paper, the authors show that DTCs persist despite functional, antigen-specific CD8+ T cells being present simultaneously in the body and set to investigate what determines the ability of DTCs to evade immune surveillance. Through a series of in vitro and in vivo experiments, Goddard et al. were able to show that although DTCs downregulate MHC I expression as previously postulated, the reduction in MHC I expression is insufficient to fully evade identification by tumour antigen-specific T-cell receptor cells. According to this paper, the evasion of immune surveillance could be explained by the relative scarcity of the two types of cells, which reduces the likelihood of DTC-T cell interactions. Boosting the number of T cells through either T cell based vaccines or adoptive cell transfer using CAR T cells targeting CD19 or HER2, a breast cancer-relevant antigen, effectively eliminated most DTCs in mouse models. However, a small fraction of DTCs persisted in their experiments.
Findings from this study might open a new therapeutic avenue for preventing breast cancer recurrence. Future studies might look into identifying DTC-specific antigens and optimising the T Cell delivery strategies and T cell – DTC ratio for complete elimination of DTCs.
