B cell-related gene signature and cancer immunotherapy response

Background: B lymphocytes have multifaceted functions in the tumour microenvironment, and their prognostic role in human cancers is controversial. Here we aimed to identify tumour microenvironmental factors that influence the prognostic effects of B cells.

Methods: We conducted a gene expression analysis of 3585 patients for whom the clinical outcome information was available. We further investigated the clinical relevance for predicting immunotherapy response.

Results: We identified a novel B cell-related gene (BCR) signature consisting of nine cytokine signalling genes whose high expression could diminish the beneficial impact of B cells on patient prognosis. In triple-negative breast cancer, higher B cell abundance was associated with favourable survival only when the BCR signature was low (HR = 0.68, p = 0.0046). By contrast, B cell abundance had no impact on prognosis when the BCR signature was high (HR = 0.93, p = 0.80). This pattern was consistently observed across multiple cancer types including lung, colorectal, and melanoma. Further, the BCR signature predicted response to immune checkpoint blockade in metastatic melanoma and compared favourably with the established markers.

Conclusions: The prognostic impact of tumour-infiltrating B cells depends on the status of cytokine signalling genes, which together could predict response to cancer immunotherapy.