Tumour-reactive B cells and antibody responses after allogeneic haematopoietic cell transplantation

Abstract

For many high-risk haematologic malignancies, such as acute myeloid leukaemia, the success of therapy relies mainly on invoking a curative antitumour immune response. This can be achieved by inducing a graft-versus-leukaemia response following allogeneic haematopoietic cell transplantation. While the contribution of T cells and natural killer cells to graft-versus-leukaemia responses is established, the contribution of B cells and antibodies is relatively unexplored. This article reviews what is known about the contribution of B cells and tumour-specific antibody responses to a successful graft-versus-leukaemia response leading to eradication of the tumour.

Keywords: B lymphocytes; allogeneic hematopoietic stem cell transplantation; graft versus leukemia response; immunotherapy; tumor specific antibodies.

Figure 1

Immune reconstitution and relapse of acute myeloid leukaemia (AML). Immune reconstitution dynamics after allogeneic haematopoietic cell transplantation (HCT) differ between immune cell subsets. Innate cells such as neutrophils and natural killer (NK) cells recover within weeks. Reconstitution of numeric B cells and CD8 T cells occurs within approximately 6 months, although their subset compositions may be altered for much longer. Reconstitution of CD4 T cells, particularly naïve CD4 and naïve CD8 T cells, is slow and often incomplete. The majority of AML relapses occur in the first 6 months after allogeneic HCT, at a time when the adaptive immune system has not yet fully recovered.

Figure 2

B cells in graft-versus-leukaemia responses. B cells can exert antitumour effects via a number of mechanisms. (1) Antibodies secreted by plasma cells can induce antibody-dependent cellular cytotoxicity, antibody-dependent cellular phagocytosis, complement-dependent cytotoxicity or can be directly cytotoxic. (2) B cells can act as antigen-presenting cells when cognate antigens bound to membrane-expressed immunoglobulin are internalized, processed and presented in the context of major histocompatibility complex (MHC) to T cells. (3) B cells can modulate the tumour microenvironment and antitumour immune responses via the secretion of pro-inflammatory cytokines, such as interleukin (IL)-2, tumour necrosis factor-α, IL-6, IL-12, migration inhibitory factor and interferon-γ. (4) B cells can produce cytotoxic granzyme B (GZB); Mϕ, macrophage.