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Potently anti-tumor T cells gather in subset of lung-to-brain metastases

Johanna Joyce, Ludwig Cancer Research Lausanne
Johanna Joyce

Among brain cancer patients, responses to checkpoint blockade immunotherapies are more commonly associated with brain metastases than with primary brain tumors, like gliomas. To explore the immunology underlying this variability, researchers led by Ludwig Lausanne’s Johanna Joyce and former PhD student Vladimir Wischnewski conducted a comprehensive, integrated analysis on a single cell and bulk population level of circulating and tumor-infiltrating T cells from 84 individuals with primary brain tumors and brain metastases, and 44 others with primary lung and breast tumors. They reported in a Nature Cancer paper in May that a subgroup of patients with brain metastases (mostly from the lung), but not gliomas, had significant infiltration of potentially anti-cancer T cells in their tumors. Infiltrating T cells expressed CXCL13 and CD39, proteins that are associated with response to immunotherapy. These potently reactive anti-tumor T cells accumulated in the brain tumors of these individuals in numbers comparable to those seen in primary lung malignancies. All other brain tumors, meanwhile, had low levels of these cells, similar to those seen in primary breast tumors. The findings show that T cell infiltration does occur in some brain metastases and suggest the phenomenon could be exploited for patient stratification in the management of therapy for brain cancers.

Phenotypic diversity of T cells in human primary and metastatic brain tumors revealed by multiomic interrogation
Nature Cancer, 2023 May 22

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