A B-cell or a key player? The different roles of B-cells and antibodies in melanoma.

The B-cell system plays an important role in the melanoma immune response; however, consensus has yet to be reached in many facets. Here, we comprehensively review human studies only, due to fundamental differences in the humoral response with animal models. Tumour-infiltrating B-cells are associated with contradictory prognostic values, reflecting a lack of agreement between studies on cell subset classification and differences in the markers used, particularly the common use of a single marker not differentiating multiple subsets.

Identifying neoantigens for use in immunotherapy.

This review focuses on the types of cancer antigens that can be recognised by the immune system and form due to alterations in the cancer genome, including cancer testis, overexpressed and neoantigens. Specifically, neoantigens can form when cancer cell-specific mutations occur that result in alterations of the protein from 'self'. This type of antigen can result in an immune response sufficient to clear tumour cells when activated.

Antigen depot is not required for alum adjuvanticity.

Alum adjuvants have been in continuous clinical use for more than 80 yr. While the prevailing theory has been that depot formation and the associated slow release of antigen and/or inflammation are responsible for alum enhancement of antigen presentation and subsequent T- and B-cell responses, this has never been formally proven. To examine antigen persistence, we used the chimeric fluorescent protein EαGFP, which allows assessment of antigen presentation in situ, using the Y-Ae antibody.

Characterization of CD4+ T-cell-dendritic cell interactions during secondary antigen exposure in tolerance and priming.

Despite the recent advances in our understanding of the dynamics of the cellular interactions associated with the induction of immune responses, comparatively little is known about the in vivo behaviour of antigen-experienced T cells upon secondary antigen exposure in either priming or tolerance. Such information would provide an insight into the functional mechanisms employed by memory T cells of distinct phenotypes and provide invaluable knowledge of how a specific tolerogenic or immunogenic state is maintained. Using real-time imaging to follow the in vivo motility of naïve, primed and tolerized CD4(+) T cells and their interactions with dendritic cells (DCs), we demonstrate that each of these distinct functional phenotypes is associated with specific patterns of behaviour.

TNF-blocking therapies: an alternative mode of action?

Despite expanding use of drugs blocking tumour necrosis factor (TNF), their precise mechanisms of action remain unclear. Early assumptions that they act by direct neutralization of the toxic inflammatory effects of TNF might be too simplistic because they explain neither the range of effects observed nor the varying properties of different TNF-blocking agents. Recent studies have demonstrated a key role for mast cell-derived TNF in the increase in lymph node size and the organizational complexity that accompanies a developing immune response.