Despite evidence that antitumor immunity can be protective against renal cell carcinoma (RCC), few patients respond objectively to immunotherapy and the disease is fatal once metastases develop. We asked to what extent combinatorial immunotherapy with Adenovirus-encoded murine TNF-related apoptosis-inducing ligand (Ad5mTRAIL) plus CpG oligonucleotide, given at the primary tumor site, would prove efficacious against metastatic murine RCC. To quantitate primary renal and metastatic tumor growth in mice, we developed a luciferase-expressing Renca cell line, and monitored tumor burdens via bioluminescent imaging. Orthotopic tumor challenge gave rise to aggressive primary tumors and lung metastases that were detectable by day 7. Intra-renal administration of Ad5mTRAIL+CpG on day 7 led to an influx of effector phenotype CD4 and CD8 T cells into the kidney by day 12 and regression of established primary renal tumors. Intra-renal immunotherapy also led to systemic immune responses characterized by splenomegaly, elevated serum IgG levels, increased CD4 and CD8 T cell infiltration into the lungs, and elimination of metastatic lung tumors. Tumor regression was primarily dependent upon CD8 T cells and resulted in prolonged survival of treated mice. Thus, local administration of Ad5mTRAIL+CpG at the primary tumor site can initiate CD8-dependent systemic immunity that is sufficient to cause regression of metastatic lung tumors. A similar approach may prove beneficial for patients with metastatic RCC.

Identifying patient characteristics associated withachieving treatment response to biologics in patients with psoriasis could prevent expensive switching between biologics. The aim of this study was to identifypatient characteristics that predict the efficacy of treatment for biologics that inhibit tumour necrosis factor-α, interleukin-12/-23, and -17A. The study investigated biologic-naïve patients from the DERMBIO registry treated with adalimumab, etanercept, infliximab, secukinumab, or ustekinumab. Multivariable logistic models were conducted to assess associations between patient characteristics and treatment response. A total of 2,384 patients were included (adalimumab n = 911; etanercept n = 327; infliximab n = 152; secukinumab n = 323; ustekinumab n = 671). Smoking (odds ratio 0.74; 95% confidence interval (CI) 0.56–0.97; p = 0.03) and higher bodyweight (odds ratio 0.989; 95% CI 0.984–0.994; p < 0.001) reduced the odds of achieving response defined as Psoriasis Area and Severity Index ≤2.0 after 6 months of treatment. In conclusion, higher bodyweight and smoking were associated with a reduced probability of treatment response for tumour necrosis factor-α inhibitors, ustekinumab, and secukinumab.

<b><i>Background:</i></b> Psoriasis flare-ups and the change of morphology from nonpustular to pustular psoriasis following tapering and withdrawal of systemic corticosteroids have been reported. Despite these risks, systemic corticosteroids are still widely prescribed for patients with psoriasis, but the knowledge about psoriasis flare-ups and whether the physicians take precautions during these treatments is limited. <b><i>Methods:</i></b> We conducted a questionnaire study among all dermatologists, gastroenterologists and rheumatologists in Denmark who work at a hospital or in a private practice to investigate the use, opinion and experience with oral, intramuscular and intra-articular corticosteroids in the treatment of patients with psoriasis. <b><i>Results:</i></b> We received answers from a total of 248 physicians. Compared with oral and intramuscular corticosteroids, intra-articular corticosteroids were the most reported treatment in patients with psoriasis and only used by the rheumatologists. It was mainly the dermatologists and rheumatologists who had observed psoriasis flare-ups following treatment with oral, intramuscular and intra-articular corticosteroids. Half of the dermatologists (50%) and a fourth of the rheumatologists (29%) had observed at least one psoriasis flare-up following treatment with oral corticosteroids. About 10% of both the dermatologists and the rheumatologists had observed at least one psoriasis flare-up following treatment with intramuscular and/or intra-articular corticosteroids. Overall, 44% of the respondents took precautions, when they treated a patient with psoriasis with oral, intramuscular and intra-articular corticosteroids. <b><i>Conclusion:</i></b> The results from the questionnaire indicate that systemic corticosteroids for patients with psoriasis can cause flare-ups and should be used with care.

A nontoxic, iodoacetamide-modified cobratoxin derivative (CAM-NTX) induced resistance to experimental allergic encephalomyelitis (EAE) in guinea pigs. Resistance was retained after trypsin digestion and shown to reside in N-terminal and central peptides of CAM-NTX. A similarly modified protein cardiotoxin (CAM-CTX), representative of proteins homologous with cobratoxin, was not immunosuppressive. Depressed clinical symptoms in EAE-resistant animals correlated with reduced lymphocytic infiltration of the brain. Antibody to myelin basic protein (MBP) was reduced in immunosuppressed animals. The immunoinhibitory determinants in CAM-NTX may mimic immune response suppressor proteins (SIRS-alpha 7) and the EAE-resistance region of MBP.

Facial and genital psoriasis impairs quality of life and is challenging to treat because of increased percutaneous penetration and, consequently, increased risk of adverse effects. Topical calcineurin inhibitors are recognized as a valid off-label treatment for these sensitive skin areas, but data on safety and efficacy are limited. This systematic review of the literature included 24 of 3,322 studies (5 randomized controlled trials, 9 open-label studies, 2 case series and 8 case reports). All studies demonstrated positive efficacy; 11 studies found statistically significant reductions in psoriasis severity. Local stinging, burning and itching were the most common short-term adverse effects and were reported in 18 studies. Topical calcineurin inhibitors appear to have an important role in the treatment of facial and genital psoriasis. The drugs are effective and generally well-tolerated with few adverse effects.