Identification of the cis­molecular neighbours of the immune checkpoint protein B7­H4 in the breast cancer cell­line SK­BR­3 by proteomic proximity labelling.

The immune checkpoint protein B7­H4 plays an important role in the positive as well as the negative regulation of immune T­cell responses. When expressed on cancer cells, B7­H4 inhibits T­cell activity, and numerous types of cancer cells use upregulation of B7­H4 as a survival strategy. Thus, B7­H4 is a potential target for anticancer drug therapy. Unfortunately, the cell biology of this molecule has yet to be fully elucidated. Even basic properties, such as the nature of B7­H4 interactors, are controversial. In particular, the cis­interactors of B7­H4 on cancer cell plasma membranes have not been investigated to date. The present study used a proteomic proximity­labelling assay to investigate the molecular neighbours of B7­H4 on the surface of the human breast cancer cells SK­BR­3. By comparison to a comprehensive proteome analysis of SK­BR­3 cells, the proximity method detected a relatively small number of low abundance plasma membrane proteins highly enriched for proteins known to modulate cell adhesion and immune recognition. It may be inferred that these molecules contribute to the immunosuppressive behaviour that is characteristic of B7­H4 on cancer cells.

Open-label, pilot study examining sequential therapy with oral tacrolimus and topical tacrolimus for severe atopic dermatitis.

BACKGROUND: Systemic treatment options for generalized atopic dermatitis (AD) are limited. To our knowledge, there have been no prospective trials examining the use of oral tacrolimus, a calcineurin inhibitor, in AD. OBJECTIVES: We assessed the safety and efficacy of sequential therapy with oral tacrolimus and topical tacrolimus in the treatment of generalized AD using the Eczema Area and Severity Index and the Physician Global Assessment scores as the primary end points. METHODS: Twelve patients with AD covering at least 50% body surface area were enrolled. Patients in both phases of the study received sequential therapy with oral and topical tacrolimus over a 14-week treatment period. Eczema Area and Severity Index, Physician Global Assessment, and pruritus scores were calculated at each study visit. RESULTS: Patients recorded a 67% improvement in the Eczema Area and Severity Index score, a 45% improvement in the Physician Global Assessment score, and a 69% reduction in the pruritus score. LIMITATIONS: This investigator-initiated, open-label, single-center, proof-of-concept study lacks a large sample size and placebo control group. CONCLUSION: Sequential therapy with oral tacrolimus and topical tacrolimus may be an effective treatment for AD. A large, randomized control study is warranted.