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Charting the immunogenomic landscapes of brain metastases

Johanna Joyce, Ludwig Cancer Research Lausanne
Johanna Joyce
Angel Alvarez-Prado, Ludwig Cancer Research Lausanne
Ángel Álvarez-Prado

A study led by Ludwig Lausanne’s Johanna Joyce and Ángel Álvarez-Prado combined a panoply of molecular profiling and imaging techniques to explore whether immune cells in breast and lung cancer brain metastases (BrM) behave differently depending on the mutations present in the host tumor’s cells. Brain metastases are the most common type of brain tumors and are associated with poor outcomes, with lung and breast cancer patients surviving just 7 to 9 months, respectively, following diagnosis. Clinicians are increasingly using genetic analysis to personalize treatment of these tumors and while immunotherapeutic approaches to their treatment—though long ineffective—are now beginning to show promise, little was known about how their genomic landscapes affect their heterogeneous immune microenvironments. Johanna, Ángel and their colleagues reported in a January issue of Cell Reports Medicine that TP53 mutant lung-BrMs are more infiltrated with immune cells and have more activated killer T cells as well as more immunosuppressive tumor-associated macrophages than those lacking such mutations. In breast-BrMs, hypermutation—seen in 44% of the metastases the researchers analyzed—was associated with greater numbers of infiltrating killer T cells into the tumor and a generally more inflamed immune microenvironment. These findings, the authors suggest, should contribute to future efforts to devise immunotherapies that are tailored to better fit the immunogenomic landscapes of brain metastases.

Immunogenomic analysis of human brain metastases reveals diverse immune landscapes across genetically distinct tumors
Cell Reports Medicine, 2023 January 17

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