Development of HPV-associated cancers not only depends on efficient negative regulation of cell cycle control that supports the accumulation of genetic damage, but also relies on immune evasion that enable the virus to go undetected for long periods of time. In this way, HPV-related tumors usually present MHC class I down-regulation, impaired antigen-processing ability, avoidance of T-cell mediated killing, increased immunosuppression due to Treg infiltration and secrete immunosuppressive cytokines. Thus, these are the main obstacles that immunotherapy has to face in the treatment of HPV-related pathologies where a number of different strategies have been developed to overcome them including new adjuvants. Although antigen-specific immunotherapy induced by therapeutic HPV vaccines was proved extremely efficacious in pre-clinical models, its progression through clinical trials suffered poor responses in the initial trials. Later attempts seem to have been more promising, particularly against the well-defined precursors of cervical, anal or vulvar cancer, where the local immunosuppressive milieu is less active. This review focuses on the advances made in these fields, highlighting several new technologies (such as mRNA vaccine, plant-derived vaccine). The most promising immunotherapies used in clinical trials are also summarized, along with integrated strategies, particularly promising in controlling tumor metastasis and in eliminating cancer cells altogether.After the early promising clinical results, the development of therapeutic HPV vaccines need to be implemented and applied to the users in order to eradicate HPV-associated malignancies, eradicating existing perception (after the effectiveness of commercial preventive vaccines) that we have already solved the problem.
Background: Plaque psoriasis (PP) and seborrheic dermatitis (SD) are chronic inflammatory skin diseases with similar clinical and pathological features. Differential diagnosis can be difficult, especially when particular skin areas of the face are involved. Reflectance confocal microscopy (RCM) has been demonstrated to be useful for ‘real-time' diagnosis of skin inflammatory diseases. Objective: To define distinctive confocal criteria of SD and to evaluate the usefulness of this technique for noninvasive differential diagnosis with PP. Methods: A total of 40 patients affected by PP and 19 patients by SD involving the face were recruited and subjected to RCM evaluation. Univariate and adjusted odds ratios were calculated. Discriminant functions were used to plot ROC curves. Results: The results disclosed specific patterns for SD and PP. The following distinctive confocal features for SD have been identified: spongiosis, dermal inflammation and horizontal orientation of dilated blood vessels. Conclusion: SD has a specific and easily recognizable confocal pattern supporting clinical differentiation with PP.
The combination of silymarin and S-MSM can be useful in managing symptoms and condition of rosacea skin, especially in the rosacea subtype 1 erythemato-telangiectatic phase. The action can be considered multicentric and multiphase because of the direct modulating action on cytokines and angiokines normally involved and up-regulated in the case of such skin condition.
Background. The therapeutic management of psoriasis includes conventional treatments as well as the new generation of highly effective TNF-α inhibitors. However, psoriasis has proven to be a complex therapeutic challenge and treatment failures are not uncommon. Thus, laboratory biomarkers of disease progression/therapeutic efficacy may greatly help in the clinical management of psoriasis. Aims. To identify laboratory biomarkers for clinical management and therapeutic monitoring of psoriasis. Methods. An observational study performed on 59 patients, presenting moderate to severe psoriasis, undergoing treatment with anti-TNF-α agents (etanercept, adalimumab, and infliximab). Soluble and cellular immune/inflammatory parameters were assessed at baseline and after 12 and 24 weeks of treatment. Results. Clinical efficacy was achieved in 88% of the subjects at 12 weeks, reaching 90% after 24 weeks. IL-6 and IL-22, which were elevated at baseline, were significantly reduced, in association with a significant decrease of CLA+ T cells and an increase of Treg lymphocytes. T, B, and NK cell subsets and T cell response to recall antigens did not show any evidence of immune suppression. Conclusions. Immune/inflammatory parameters including IL-6 and IL-22, CLA+ T cells, and Treg lymphocytes may prove to be valuable laboratory tools for the clinical and therapeutic monitoring of psoriasis.
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