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A single gene expressed in fibroblastic reticular cells predicts response to cancer immunotherapy

D. Biasci,S. Tavaré,James E. D. Thaventhiran

Published 2020 in bioRxiv

ABSTRACT

While the role of T cells in immune response to cancer is well established, the role of B cells remains more controversial. Recently, it was reported that expression of B cell specific genes inside tumours is associated with response to immune checkpoint blockade (ICB), thus suggesting an unappreciated biological role for B cells in promoting ICB response. However, association between B cell gene expression and ICB response was not statistically significant when other immune populations, including CD8+ T cells, were taken into account. For this reason, it remains unclear whether B cells are associated with ICB response independently of CD8+ T cell infiltration, a validated predictor of immunotherapy response strongly correlated with B cells. Two complementary studies did not address this issue, because they described predictive signatures containing genes expressed in CD8+ T cells, as well as other immune cell types. Helmink et al. acknowledge this limitation of their work, attributing it to limited sample size, and call for larger studies to clarify the point. By conducting the largest gene expression study of ICB response to date, here we show that: 1) pre-treatment expression of B cell genes is indeed associated with ICB response; 2) such association is independent of CD8+ T cells; 3) the association can be completely explained by a single gene expressed in fibroblastic reticular cells (FRCs). We further validate this last finding in three independent cohorts of patients treated with ICB.

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