Enolase 1 of Candida albicans binds human CD4+ T cells and modulates naïve and memory responses

To obtain a better understanding of the biology behind life-threatening fungal infections caused by Candida albicans, we recently conducted an in silico screening for fungal and host protein interaction partners. We report here that the extracellular domain of human CD4 binds to the moonlighting protein enolase 1 (Eno1) of C. albicans as predicted bioinformatically. By using different anti-CD4 monoclonal antibodies, we determined that C. albicans Eno1 (CaEno1) primarily binds to the extracellular domain 3 of CD4. Functionally, we observed that CaEno1 binding to CD4 activated lymphocyte-specific protein tyrosine kinase (LCK), which was also the case for anti-CD4 monoclonal antibodies tested in parallel. CaEno1 binding to naïve human CD4⁺ T cells skewed cytokine secretion toward a Th2 profile indicative of poor fungal control. Moreover, CaEno1 inhibited human memory CD4⁺ T-cell recall responses. Therapeutically, CD4⁺ T cells transduced with a p41/Crf1-specific T-cell receptor developed for adoptive T-cell therapy were not inhibited by CaEno1 in vitro. Together, the interaction of human CD4⁺ T cells with CaEno1 modulated host CD4⁺ T-cell responses in favor of the fungus. Thus, CaEno1 mediates not only immune evasion through its interference with complement regulators but also through the direct modulation of CD4⁺ T-cell responses.     

Future of combination therapy with dabrafenib and trametinib in metastatic melanoma

Introduction: Combination therapy with BRAF and MEK inhibitors is a recommended treatment strategy for metastatic melanoma patients with BRAF^V600 mutations. This treatment provides significant response rates and little added toxicity, with relatively improved survival outcomes compared to RAF/MEK inhibitor monotherapy and chemotherapy.

Areas covered: This review covers the pharmacology, efficacy, and toxicity data derived from clinical studies of dabrafenib, trametinib, and the combination thereof. The major downfall of combiDT is the limited durability of response, which is largely due to acquired resistance in the MAPK pathway.

Expert opinion: Future directions of combiDT concentrate on further combinations with immunotherapy or other targeted inhibitors, referred to triple-agent therapy, which may be essential to improving durability of responses and overcoming resistance.     

Optical optimization of double-side-textured monolithic perovskite–silicon tandem solar cells for improved light management

Tandem configuration-containing perovskite and silicon solar cells are promising candidates for realizing a high power conversion efficiency of 30% at reasonable costs. Silicon solar cells with planar front surfaces used in tandem devices cause high optical losses, which significantly affects their efficiency. Moreover, some studies have explored the fabrication of perovskites on textured silicon cells. However, due to improper texturing, light trapping is not ideal in these devices, which reduces the efficiency. In this work, we optimized the pyramid height of textured silicon cells and efficiently characterized them to achieve enhanced light trapping. Two different kinds of perovskites, namely, Cs_0.17FA_0.6Pb(Br_0.17I_0.7)₃ and Cs_0.25FA_0.6Pb(Br_0.20I_0.7)₃ with wide bandgaps were conformally deposited on textured silicon cells, and the performance of these flat and fully textured tandem devices was numerically analyzed. The thickness of each layer in the tandem cell was optimized in a way to ensure a perfect current match between the top perovskite and bottom silicon subcells. The results indicated that the textured tandem configuration enhances light absorption over a broad spectral range due to the optimized pyramid height compared to flat surfaces. Eventually, the photovoltaic parameters of the proposed tandem cell were compared with the already existing structures, and our design supports large values of open circuit voltage (V_oc) = 1.78 V, short circuit current density (J_sc) = 20.09 mA cm⁻², fill factor (FF) = 79.01%, and efficiency (η) = 28.20% compared to other kinds of tandem solar cells.

Tandem configuration-containing perovskite and silicon solar cells are promising candidates for realizing a high power conversion efficiency of 30% at reasonable costs.