Trichophyton tonsurans‐induced kerion celsi with decreased defensin expression and paradoxically increased interleukin‐17A production

We report a case of kerion celsi due to Trichophyton tonsurans. An 18‐year‐old male student judo practitioner had alopecic patches, black dots and subcutaneous abscesses on the right temporal region. The damaged hair represented endothrix infection with T. tonsurans, as assessed by mycological examinations. He was treated with oral itraconazole without any therapeutic effect, followed by terbinafine with good effect. A skin biopsy showed neutrophil, lymphocyte and histiocyte infiltration into the dermis and subcutaneous tissue with abscesses around a number of dilated hair follicles. Immunostaining showed that the expression level of human β‐defensin 2 (HBD‐2) was decreased in the epidermis of the alopecic and adjacent skin. Because interleukin (IL)‐17A generally induces HBD‐2 production by epidermal keratinocytes, we also immunohistochemically investigated IL‐17A expression. Unexpectedly, many IL‐17A‐bearing cells were found around destructed hair follicles, indicating that IL‐17A expression was not attenuated, but rather increased in the skin lesion. Our case suggests that IL‐17A‐upregulated antimicrobial peptide expression is disordered in kerion celsi, and severe inflammation with IL‐17A may cause tissue damage and resultant scar.     

Anti‐tumor effects of mAb against l‐type amino acid transporter 1 (LAT1) bound to human and monkey LAT1 with dual avidity modes

l ‐Type amino acid transporter 1 (LAT1) disulfide linked to CD98 heavy chain (hc) is highly expressed in most cancer cells, but weakly expressed in normal cells. In the present study, we developed novel anti‐LAT1 mAbs and showed internalization activity, inhibitory effects of amino acid uptake and cell growth and antibody‐dependent cellular cytotoxicity, as well as in vivo antitumor effects in athymic mice. Furthermore, we examined the reactivity of mAbs with LAT1 of Macaca fascicularis to evaluate possible side‐effects of antihuman LAT1 mAbs in clinical trials. Antihuman LAT1 mAbs reacted with ACHN human and MK.P3 macaca kidney‐derived cells, and this reactivity was significantly decreased by siRNAs against LAT1. Macaca LAT1 cDNA was cloned from MK.P3, and only two amino acid differences between human and macaca LAT1 were seen. RH7777 rat hepatoma and HEK293 human embryonic kidney cells expressing macaca LAT1 were established as stable transfectants, and antihuman LAT1 mAbs were equivalently reactive against transfectants expressing human or macaca LAT1. Dual (high and low) avidity modes were detected in transfectants expressing macaca LAT1, MK.P3, ACHN and HCT116 human colon cancer cells, and K_A values were increased by anti‐CD98hc mAb, suggesting anti‐LAT1 mAbs detect an epitope on LAT1‐CD98hc complexes on the cell surface. Based on these results, LAT1 may be a promising anticancer target and Macaca fascicularis can be used in preclinical studies with antihuman LAT1 mAbs.     

Supplementation of l‐arginine boosts the therapeutic efficacy of anticancer chemoimmunotherapy

Myeloid‐derived suppressor cells (MDSCs) play a crucial role in immunosuppression in tumor‐bearing hosts. MDSCs express arginase‐I and indoleamine 2,3‐dioxygenase; they suppress T‐cell function by reducing the levels of l ‐arginine and l ‐tryptophan, respectively. We examined the anticancer effects of supplementation of these amino acids in CT26 colon carcinoma‐bearing mice. Oral supplementation of l ‐arginine or l ‐tryptophan (30 mg/mouse) did not affect tumor growth, whereas oral supplementation of d ‐arginine was lethal. Supplementation of l ‐arginine showed a tendency to augment the efficacy of cyclophosphamide (CP). CP reduced the proportions of granulocytic MDSCs and increased the proportions of monocytic MDSCs in the spleen and tumor tissues of CT26‐bearing mice. l ‐Arginine supplementation alone did not affect the MDSC subsets. CP treatment tended to reduce the plasma levels of l ‐arginine in CT26‐bearing mice and significantly increased the number of tumor‐infiltrating CD8⁺ T cells. In addition, l ‐arginine supplementation significantly increased the proportions of tumor peptide‐specific CD8⁺ T cells in draining lymph nodes. Importantly, additional supplementation of l ‐arginine significantly increased the number of cured mice that were treated with CP and anti‐PD‐1 antibody. Totally, l ‐arginine supplementation shows promise for boosting the therapeutic efficacy of chemoimmunotherapy.