Tumour immunology

Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion.Dong, H. et al. Nature Med. 24 June 2002 (DOI 10.1038/nm730)

Like viruses, tumour cells use many mechanisms to evade host immune responses. Here, Dong et al. show that most human cancers express the co-stimulatory molecule B7-H1, whereas normal tissues do not, with the exception of macrophages. When activated T cells interact with tumour-associated B7-H1, the T cells die by apoptosis, which seems to be mediated by both interleukin-10 and Fas ligand. This indicates that another method that is used by tumour cells to avoid recognition and destruction by the immune system involves the deletion of activated T cells at the tumour site. This work has implications for the use of adoptive T-cell therapy to treat cancer. It might be possible to enhance T-cell-mediated killing of B7-H1-positive tumour cells by blockade of B7-H1 using monoclonal antibodies or soluble inhibitors.

Innate immunity

Activation of Drosophila Toll during fungal infection by a blood serine protease.Ligoxygakis, P., Pelte, N., Hoffmann, J. A. & Reichart, J.-M. Science 297, 114–116 (2002)

In Drosophila, a cleaved form of Spaetzle is the extracellular ligand for the Toll pathway in both embryonic development and immune responses to fungal pathogens. However, the upstream events that link infection to the cleavage of Spaetzle remain undefined. Here, Ligoxygakis et al. show — by screening for mutants that suppress the constitutive activation of the anti-fungal pathway in Necrotic mutant flies — that persephone (psh), a serine protease, is a central component of the fungal-mediated activation of Toll. The upstream pattern-recognition molecule that activates the protease function of psh remains to be identified.

HIV

Epistatic interaction between KIRDS1 and HLA-B delays the progression to AIDS.Martin, M. P. et al. Nature Genet. 22 July 2002 (DOI 10.1038/ng934)

Natural killer (NK)-cell responses are regulated by the balance of signals that are received from activating and inhibitory receptors. Killer immunoglobulin-like receptors (KIRs) are expressed on human NK cells and interact with HLA class I molecules on target cells. In this study, Martin et al. report that the activating KIR allele KIRDS1, in association with HLA-B Bw4-80Ile — an HLA-B allele that has an isoleucine residue at position 80 — is associated with a delay in the development of AIDS in HIV-1-positive patients. The absence of HLA-B Bw4-80Ile is associated with a more rapid progression to AIDS, whereas the absence of KIRDS1 has no effect. The identification of this interaction might provide a new approach for the development of vaccines or therapeutic agents.