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Translational Therapeutics

B cell-related gene signature and cancer immunotherapy response

Abstract

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.

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Fig. 1: Relation between B cell lineage abundance score (B.cell) and T lymphocytes module (T.cell).
Fig. 2: Cytokine signalling genes modulating B lymphocytes prognosis.
Fig. 3: Survival analysis of B cell-related gene (BCR) signature in the validation cohorts.
Fig. 4: B cell-related gene (BCR) signature association with anti-PD1 and anti-CTLA4 immune checkpoint blockade response.

Data availability

All original data sets used in this article are publicly available with accession codes provided in Supplemental Table 5.

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Funding

This research was partially supported by the National Institutes of Health grant R01 CA222512.

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Contributions

AL and RL contributed to the study concept and design. AL contributed to the acquisition and analyses of data. All authors interpreted the data and did the manuscript drafting and critical revision. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Ruijiang Li.

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Lundberg, A., Li, B. & Li, R. B cell-related gene signature and cancer immunotherapy response. Br J Cancer 126, 899–906 (2022). https://doi.org/10.1038/s41416-021-01674-6

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