Tumor-associated macrophages (TAMs) may have an important role in tumor immunity. We studied the activation state of TAMs in cutaneous SCC, the second most common human cancer. CD163 was identified as a more abundant, sensitive, and accurate marker of TAMs when compared with CD68. CD163(+) TAMs produced protumoral factors, matrix metalloproteinases 9 and 11 (MMP9 and MMP11), at the gene and protein levels. Gene set enrichment analysis (GSEA) was used to evaluate M1 and M2 macrophage gene sets in the SCC genes and to identify candidate genes in order to phenotypically characterize TAMs. There was coexpression of CD163 and alternatively activated "M2" markers, CD209 and CCL18 (chemokine (C-C motif) ligand 18). There was enrichment for classically activated "M1" genes in SCC, which was confirmed in situ by colocalization of CD163 and phosphorylated STAT1 (signal transducer and activator of transcription 1), IL-23p19, IL-12/IL-23p40, and CD127. Also, a subset of TAMs in SCC was bi-activated as CD163(+) cells expressed markers for both M1 and M2, shown by triple-label immunofluorescence. These data support heterogeneous activation states of TAMs in SCC, and suggest that a dynamic model of macrophage activation would be more useful to characterize TAMs.
Psoriasis vulgaris is a complex disease characterized by alterations in growth and differentiation of epidermal keratinocytes as well as marked increase in leukocyte populations. Lesions are known to contain alterations in mRNAs encoding more than 1000 products, but only a very small number of these transcripts have been localized to specific cell types or skin regions. In this study, we used laser capture microdissection (LCM) and gene array analysis to study the gene expression of cells in lesional epidermis and dermis, compared with corresponding non-lesional resions. Using this approach, we detected >1800 differentially expressed gene products in the epidermis or dermis of psoriasis lesions. These results established sets of genes that are differentially expressed between epidermal and dermal compartments, as well as between non-lesional and lesional psoriasis skin. One of our findings involved the local production of CCL19, a lymphoid organizing chemokine, and its receptor CCR7 in psoriatic dermal aggregates, along with the presence of gene products LAMP3/DC-LAMP and CD83, which typify mature DCs. Gene expression patterns obtained with LCM and microarray analysis along with T cell and DC detection by immune staining suggest a possible mechanism for lymphoid organization via CCL19/CCR7 in diseased skin.
IMPORTANCE Recent concerns regarding repetitive use of general anesthesia in children younger than 3 years have placed greater importance on the controversy surrounding the timing of the initiation of port-wine stain (PWS) laser treatment. OBJECTIVE To evaluate the use of PWS treatments at the age of 1 year or younger in the office setting without general anesthesia. DESIGN, SETTING, AND PARTICIPANTS Retrospective cohort study based on medical record reviews at a single, high-volume laser center for children who started pulsed dye laser treatment at the age of 1 year or younger for their PWS between 2000 and 2017. The data cutoff was at 1 year after the initial treatment to have comparable data points. MAIN OUTCOMES AND MEASURES The primary outcome was improvement of PWSs using before and after photographs, which were reviewed by 4 physicians independently and graded using the following 5-point visual analog scale (VAS): poor (grade 1: 0%-25% improvement), fair (grade 2: 26%-50% improvement), good (grade 3: 51%-75% improvement), excellent (grade 4: 76%-99% improvement), and complete (grade 5: 100% improvement) clearance. RESULTS Of the 197 patients (73 [37.1%] boys; 124 [62.9%] girls), most (149 [75.6%]) had facial lesions. The mean age at the time of first treatment was 3.38 months (range, 5-355 days) and the mean number of treatments was 9.8 (range, 2-23; median, 10). Per the mean physician VAS grading of 197 patients, 51 patients (25.9%) showed 100% clearance (mean [range] VAS score of 4.78 [4.5-5]); 81 patients (41.1%) showed 76 to 99% improvement (mean [range] VAS score of 3.91 [3.5 to <4.5]); 44 patients (22.3%) showed 51% to 75% improvement (mean [range] VAS score of 2.86 [2.5 to <3.5]); 13 patients (6.6%) showed 26% to 50% improvement (mean [range] VAS score of 2.12 [1.5 to <2.5]); and 8 patients (4.1%) showed 0 to 25% improvement (mean [range] VAS score of 0.78 [0 to <1.5]). The presence of a V1 (first branch of the trigeminal nerve [ophthalmic nerve]) lesion was associated with a statistically significantly higher clearance rate by a VAS grade of 0.55 (95% CI, 0.25-0.84; P < .001). The mean (SD) VAS grade for all patients was 3.65 (1.26), corresponding to excellent clearance. None of the patients experienced scarring or permanent pigmentary change. CONCLUSIONS AND RELEVANCE In this study, treatment of PWSs in infancy was both safe and effective. Early intervention allows for treatment without general anesthesia, maximizing the chance to achieve clearance before school age and thereby minimizing the negative outcome of PWSs for both the patient and the family.
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