T regulatory cells in B-cell malignancy - tumour support or kiss of death?

Abstract

It is well established that T regulatory (Treg) cells counteract tumour immunity. However, conflicting results describing the role of Treg cells in haematological tumours warrant further investigations to clarify the interactions between Treg cells and the tumour. B-cell malignancy derives from different stages of B-cell development and differentiation in which T cells play a profound role. The transformed B cell may still be in need of T-cell help to thrive but simultaneously they may be recognized and destroyed by cytotoxic lymphocytes. Recent reports demonstrate that Treg cells can suppress and even kill B cells as part of their normal function to rescue the body from autoimmunity. An emerging body of evidence points out that Treg cells not only inhibit tumour-specific T cells but may also have a role in suppressing the progression of the B-cell tumour. In this review, we discuss the origin and function of Treg cells and their role in patients with B-cell tumours.

Figure 1

Interactions between T cells and malignant B cells. The malignant B cells may require T helper cells for sustained growth but the helper cells may also be part of the control of malignant cells by direct cytotoxicity or by stimulating anti-tumour immunity. Helper cells can interact via T-cell receptor (TCR)/MHC-II and via co-stimulatory receptors (CSR). The malignant B cells can release substances [such as interleukin-10 (IL-10)] that promote the conversion of T helper cells into regulatory T (Treg) cells that suppress both T helper cells and cytotoxic T cells (CTL). The Treg cells can also recognize MHC-II on the B cells. If cytotoxic, they may interact via death receptors (DRs) to induce B-cell apoptosis. The CTLs recognize MHC-I on malignant B cells and induce apoptosis via DRs. GZMs, granzymes.