Low baseline levels of NK cells may predict a positive response to ipilimumab in melanoma therapy.

The introduction of immune checkpoint blockade (ICB) has been a breakthrough in the therapy of metastatic melanoma. The influence of ICB on T-cell populations has been studied extensively, but little is known about the effect on NK cells. In this study, we analysed the relative and absolute amounts of NK cells and of the subpopulations of CD56dim and CD56bright NK cells among the peripheral blood mononuclear cells (PBMCs) of 32 patients with metastatic melanoma before and under treatment with ipilimumab or pembrolizumab by flow cytometry. In 15 (47%) patients, an abnormal low amount of NK cells was found at baseline. Analysis of the subpopulations showed also low or normal baseline levels for CD56dim NK cells, whereas the baseline levels of CD56bright NK cells were either normal or abnormally high. The relative and absolute amounts of NK cells and of CD56dim and CD56bright NK cell subpopulations in patients with a normal baseline did not change under treatment. However, patients with a low baseline of NK cells and CD56dim NK cells showed a significant increase in these immune cell subsets, but the amounts remained to be lower than the normal baseline. The amount of CD56bright NK cells was unaffected by treatment. The baseline levels of NK cells were correlated with the number of metastatic organs. Their proportion increased, whereas the expression of NKG2D decreased significantly when more than one organ was affected by metastases. Low baseline levels of NK cells and CD56dim NK cells as well as normal baseline levels of CD56bright NK cells correlated significantly with a positive response to ipilimumab but not to pembrolizumab. Survival curves of patients with low amounts of CD56dim NK cells treated with ipilimumab showed a trend to longer survival. Normal baseline levels of CD56bright NK cells were significantly correlated with longer survival as compared to patients with high baseline levels. In conclusion, analysis of the amounts of total NK cells and of CD56dim and CD56bright NK cells subpopulations at baseline may help to predict the outcome of treatment with ipilimumab.

Antimicrobial Properties of Chitosan-Modified Cotton Fabric Treated with Aldehydes and Zinc Oxide Particles.

Chitosan is a natural biopolymer with a proven ability to impart textile materials with antimicrobial properties when loaded onto them. The mechanism of its bacteriological activity depends on the contact between the positive and negative charges of the amino groups located on the surface of the microbes. Unfortunately, the type of microorganisms and pH influence this action-shortcomings that can be avoided by chitosan modification and by loading its film with substances possessing antimicrobial properties. In this study, chitosan was modified with benzaldehyde and crosslinked with glutaraldehyde to form a film on the surface of cotton fabric (CB). Also, another material was obtained by including zinc oxide particles (CBZ) synthesized in situ into the chitosan coating. The performed analyses (contact angle measurement, optical and scanning electron microscopy, FTIR, XRD, and thermal analysis) evidenced the modification of the cotton fabric and the alteration of the film properties after zinc oxide inclusion. A comparison of the antimicrobial properties of the new CB with materials prepared with chitosan without benzaldehyde from our previous study verified the influence of the hydrophobicity and surface roughness of the fabric surface on the enhancement of antimicrobial activity. The microbial growth inhibition increased in the following order: fungal strain Candida lipolytica >Gram-positive bacteria Bacillus cereus >Gram-negative bacteria Pseudomonas aeruginosa. The samples containing zinc oxide particles completely inhibited the growth of all three model strains. The virucidal activity of the CB was higher against human adenovirus serotype 5 (HAdV-5) than against human respiratory syncytial virus (HRSV-S2) after 60 min of exposure. The CBZ displayed higher virucidal activity with a Δlog of 0.9 against both viruses.

The proportion of circulating CD45RO+CD8+ memory T cells is correlated with clinical response in melanoma patients treated with ipilimumab.

BACKGROUND: Immune checkpoint blockade (ICB) has been a breakthrough in the treatment of metastatic melanoma. But with only about 20-40% long-term responders and severe side-effects in about 12-17%, finding predictive markers for treatment response is of great interest. METHODS: We prospectively assessed clinical data, haematologic parameters and freshly isolated peripheral blood mononuclear cells of 30 patients treated with ipilimumab (n = 21) and pembrolizumab (n = 9) prior to the first 4 cycles with ICB and before the first tumour assessment. RESULTS: We discovered that the baseline levels of CD45RO+CD8+ T cells significantly differed among the patients. Thirteen (43%) of our patients had normal baseline levels of CD45RO+CD8+ T cells, whereas 17 (57%) patients were low on CD45RO+CD8+ T cells. The baseline levels of CD45RO+CD8+ T cells correlated significantly with the response to ipilimumab but not pembrolizumab. Patients with baseline levels of lower/equal 25% of CD45RO+CD8+ T cells did not respond to treatment with ipilimumab. Phenotyping the CD8+ T cells in patients treated with ipilimumab revealed an activated HLA-DR+CD25- phenotype, implying antigen non-specific stimulation. The levels of the HLA-DR+CD25-CD8+ T cells were significantly higher in patients with a normal baseline of CD45RO+CD8+ T cells and even increased significantly during treatment. Furthermore, proliferation of melanoma antigen recognized by T cells 1 (MART-1)-specific CD8+ T cells was not observed. Patients with normal baseline levels of CD45RO+CD8+ T cells showed a significant longer overall survival when treated with ipilimumab but not pembrolizumab. CONCLUSION: Patients with normal baseline levels of CD45RO+CD8+ T cells respond significantly more frequently to treatment with ipilimumab and the CD8+ T cells appear to be antigen non-specifically activated. The baseline level of CD45RO+CD8+ T cells represents a promising factor as biomarker for the prediction of the response to ipilimumab.