Highlights in Cancer Research: November 2023

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. Phenotypic diversity of T cells in human primary and metastatic brain tumors revealed by multiomic interrogation

Wischnewski, V. et al. Nature Cancer. 4: 908-924 (2023).
doi: doi.org/10.1038/s43018-023-00566-3.

Summary of the findings

The development of a proliferative, aggressive tumor within the brain generally reduces life expectancy to approximately one year following diagnosis. While a productive anti-tumor immune response would be required to effectively control or eliminate the cancer, brain-intrinsic mechanisms of immune-suppression can interfere with the response of tumoricidal immune cells – to protect the brain tissue from excessive neuroinflammation. Critically, how these mechanisms affect the abundance, phenotypes, and functions of brain tumor-infiltrating T cells is not yet well defined. To shed light on these processes, the authors deeply interrogated T cells in patients with different types of brain cancer, either intracranial or extracranial in origin, using a diverse panel of orthogonal analyses on single-cell, spatial, and bulk population levels. The study identified a subgroup of patients with brain metastases (BrM) that showed high accumulation of CXCL13-expressing CD39+ CD8+ potentially tumor-reactive T (pTRT) cells in their tumors. Notably, the high abundance of pTRT cells in this subset of lung-BrM samples was comparable to frequencies in primary non-small cell lung cancer, analyzed in parallel. By contrast, pTRT cells were infrequent in all other analyzed BrM tumors (including from primary breast and other lung cancer samples) and all gliomas. These low proportions of pTRT cells were similar to their analysis of primary breast cancers. These findings indicate that T cell-mediated tumor reactivity can occur within the brain, but only in a subgroup of patients.

Identifying differences in the abundance and phenotype of tumor-infiltrating T cells among patients with brain cancers of intracranial or extracranial origin. All gliomas and a subgroup of BrM samples showed low abundance of total T cells and pTRT cells, which is similar to the frequencies detected in primary (extracranial) breast cancer tissue. Another subgroup of BrM tumors were highly infiltrated with T cells, and particularly with pTRT cells, as well as type I-interferon stimulated macrophages, an immune cell composition similarly observed by the authors in primary lung tumors.

Future impact

This research provides a high-resolution analysis of T cells in patients with primary or metastatic brain cancer, an invaluable resource for the development of brain tumor-specific immunotherapies. In addition, the study highlights that patient stratification could be required for optimal treatment selection, particularly in the context of immunotherapy. BrM patients with high pTRT cell abundance may benefit from T cell-reactivation, while other subgroups would likely require strategies to additionally increase the frequencies of tumor-specific T cells. Thus, research into how to evaluate tumor-reactive T cell abundance in patients with a brain tumor in a non-invasive, or minimally invasive, manner is urgently required to achieve such patient stratification in the future.

Read more in Nature Cancer