When T Cell Inflammation Supports Choroid Plexus Tumor Growth
Choroid plexus tumors (CPTs) are rare pediatric brain tumors, and faithful preclinical models have historically been limited. In particular, benign choroid plexus papillomas (CPPs) lacked representative mouse models, making it difficult to study the biology that supports their growth.
A study from the Marino laboratory at Queen Mary University of London developed a c-MYC-driven mouse model of CPP and used it to ask a focused question: is the inflammatory infiltrate seen in these tumors simply associated with disease, or does it actively contribute to tumor growth?
c-MYC Links Tumor Growth With an Inflammatory Phenotype
Low-level c-MYC overexpression in the choroid plexus epithelium produced CPPs with high penetrance in mice. The model also reflected an inflammatory phenotype seen in human disease. In human CPT datasets, c-MYC expression was associated with inflammation-related genes, including chemokines and their receptors, and c-MYC-positive tumors showed increased infiltration by CD3+ T cells and CD68+ macrophages compared with c-MYC-negative tumors.
The increase in T cells was driven predominantly by the CD4+ compartment, and a similar inflammatory infiltrate was observed in the c-MYC-driven mouse tumors. These findings established a strong association between c-MYC expression and an inflammatory tumor microenvironment, but association alone could not show whether those immune cells were helping drive tumor growth.
Testing Whether T Cells Contribute to Tumor Growth
The investigators first crossed the c-MYC model onto an immunodeficient NOD-SCID background. Tumor incidence fell and tumors that did form were smaller, supporting a pro-tumor role for the inflammatory immune compartment in this model.
They then tested the contribution of T cells more directly in tumor-bearing mice using anti-CD3 F(ab′)2 (clone 145-2C11) or a fragment-matched hamster IgG F(ab′)2 isotype control. Anti-CD3 treatment significantly reduced CD3+ T cells in blood and spleen and produced a significant reduction in tumor area compared with the isotype-treated group1.
Further analysis showed that the treatment effect was concentrated mainly in the CD4+ T-cell compartment, including CD4+FoxP3+ cells, while no significant reduction was observed in CD8+ T cells. Macrophage infiltration was also unchanged. Together, these results provided functional in vivo support for a role of T cells in the c-MYC-driven tumor phenotype.
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Bio X Cell Relevance
As part of the study's in vivo validation, the investigators used anti-CD3 F(ab′)2 clone 145-2C11 with a hamster IgG F(ab′)2 isotype control to test the contribution of T cells to tumor growth. Anti-CD3 treatment reduced CD3+ T cells in blood and spleen and was associated with a significant reduction in tumor area1.
The study used a fragment-matched F(ab′)2 isotype control, providing a format-matched comparator for the anti-CD3 treatment. In this model, the experiment offered direct in vivo evidence that reducing the T-cell compartment altered tumor growth.
References
- Merve A, Zhang X, Pomella N, et al. c-MYC overexpression induces choroid plexus papillomas through a T-cell mediated inflammatory mechanism. Acta Neuropathologica Communications. 2019;7:95. https://doi.org/10.1186/s40478-019-0739-x