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).
The list below appears in no particular order, and the summary information has been provided by the authors unless otherwise indicated.
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5. Genetic and pharmacological modulation of DNA mismatch repair heterogeneous tumors promotes immune surveillance
Amodio, V. et al. Cancer Cell. 41 (1): 196-209. (2023).
doi: 10.1016/j.ccell.2022.12.003.
Summary of the findings
Mismatch repair (MMR) activity is a key determinant of immune response in colorectal cancer. It is worth noting that MMR deficient (MMRd) tumors are categorized as “hot” tumors due to their ability to attract a significant immune infiltrate and exhibit highly responsiveness to immune checkpoint blockade inhibitors. Conversely, MMR proficient (MMRp) tumors are generally considered immunologically “cold” and have been shown to be resistant to immunotherapy. In a subset of colorectal cancer patients, both MMRp and MMRd subpopulations coexists in the same tumor, where potentially “cold” and “hot” components share the same microenvironment. However, the impact of MMR heterogeneity on tumor immune infiltration and immune surveillance remains incompletely understood. In this paper, Amodio and colleagues attempted to address this gap by modelling MMR heterogeneity in a syngeneic murine model using MMRp and MMRd tumor cells at varying proportion. They discovered that the injection of MMRp\MMRd heterogeneous tumors in syngeneic immunocompetent mice led to a reshaping of tumor immune environment that correlated with an increase in immune surveillance. Additionally, the authors demonstrated that treatments with 6 thioguanine, an antimetabolite agent capable of selecting for cells in which the MMR machinery is unfunctional, maximized the immune response against MMR heterogeneous murine tumors.
Future impact
The study by Amodio et al highlights the potential impact of MMR heterogeneity on immune response in colorectal cancer. The findings from the murine model suggest a need for further investigation into MMR heterogeneity in human samples and propose MMR modulation as a potential strategy to enhance immune surveillance in “cold” tumors.
5. Genetic and pharmacological modulation of DNA mismatch repair heterogeneous tumors promotes immune surveillance
Summary of the findings
