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

Elin Sjöberg,Ulrika Harmenberg,John Lövrot,Arne Östman,Lars Egevad,Artur Mezheyeuski,Magnus Frödin,Per Sandström,Martin Johansson

doi:10.1038/s41416-018-0266-8

Elin Sjöberg, Ulrika Harmenberg + Show 7 more

Open Access

https://doi.org/10.1038/s41416-018-0266-8

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Abstract

BackgroundThe 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.MethodsFollowing 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.ResultsIHC 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.ConclusionThis exploratory study identifies a previously unrecognised poor-prognosis subset of RCC with high density of CD20-defined B-cells.

Highlights

Renal cell cancer (RCC) originates from the renal epithelial cells and constitutes ~3 percent of all human malignancies.[1]
Anti-angiogenic drugs currently used for the treatment of metastatic renal cell cancer (RCC) are based on clinical trials with sunitinib, pazopanib, axitinib and cabozantinib.[4,5]
Immune checkpoint regulators have been added to the armamentarium,[6] the mechanism by which they exert their antitumoural function in RCC is not fully understood

Summary

Introduction

Renal cell cancer (RCC) originates from the renal epithelial cells and constitutes ~3 percent of all human malignancies.[1]. Of all RCC, and is characterised by an inactivation of the vonHippel-Lindau gene.[3] Anti-angiogenic drugs currently used for the treatment of metastatic RCC are based on clinical trials with sunitinib, pazopanib, axitinib and cabozantinib.[4,5] More recently, immune checkpoint regulators have been added to the armamentarium,[6] the mechanism by which they exert their antitumoural function in RCC is not fully understood. T-cells are the best characterised immune cells that have an antitumour function and correlate with a favourable prognosis in many tumours.[7,8] On the contrary, B-lymphocytes are less studied and the role during tumour progression is not fully understood. This study aimed to analyse the clinical relevance of B-lymphocytes in renal cell cancer (RCC), where information on the prognostic impact is lacking

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