A minority-group of renal cell cancer patients with high infiltration of CD20+B-cells is associated with poor prognosis

Abstract

Background: The role of B-lymphocytes in solid tumours is unclear. Tumour biology studies have implied both anti- and pro-tumoural effects and prognostic studies have mainly linked B-cells to increased survival. This study aimed to analyse the clinical relevance of B-lymphocytes in renal cell cancer (RCC), where information on the prognostic impact is lacking.

Methods: Following immunohistochemistry (IHC) stainings with a CD20 antibody, density of CD20+ B-cells was quantified in an RCC discovery- and validation cohort. Associations of B-cell infiltration, determined by CD20 expression or a B-cell gene-signature, and survival was also analysed in 14 publicly available gene expression datasets of cancer, including the kidney clear cell carcinoma (KIRC) dataset.

Results: IHC analyses of the discovery cohort identified a previously unrecognised subgroup of RCC patients with high infiltration of CD20+ B-cells. The B-cell-high subgroup displayed significantly shorter survival according to uni- and multi-variable analyses. The association between poor prognosis and high density of CD20+ B-cells was confirmed in the validation cohort. Analyses of the KIRC gene expression dataset using the B-cell signature confirmed findings from IHC analyses. Analyses of other gene expression datasets, representing 13 different tumour types, indicated that the poor survival-association of B-cells occurred selectively in RCC.

Conclusion: This exploratory study identifies a previously unrecognised poor-prognosis subset of RCC with high density of CD20-defined B-cells.

Fig. 1

Variable infiltration of CD20+ cells in RCC. Immunohistochemistry staining with CD20 antibodies was used to identify tumour infiltrating B-lymphocytes in RCC patients. The majority of patients displayed no (left panel) or low infiltration (middle panel), whereas a minority of cases demonstrated high infiltration of CD20+ cells (right panel). Scale bar 100 μm

Fig. 2

Correlation of CD20 status and prognosis of RCC patients in two independent cohorts. Kaplan–Meier curves showing the overall survival of RCC patients with low or high infiltration of CD20+ cells in the discovery cohort (left panel) and the validation cohort (right panel)

Fig. 3

Associations between survival and a B-lymphocyte signature or MS4A1 expression in gene expression datasets of different tumour types. a Kaplan–Meier plot showing overall survival of clear cell RCC patients in the KIRC gene expression dataset (TCGA) with low or high B-lymphocyte gene signature score (MS4A1/CD19/PAX5). b Association of MS4A1 expression and overall survival in 14 cancer gene expression datasets from the TCGA database