Postherpetic neuralgia is a chronic pain syndrome that is often difficult to treat and can lead to a disabling disease if it is resistant to therapy. Presented here is the case of a 46-year-old ...patient with human immunodeficiency virus infection and chronic, treatment-resistant neuralgia. Postherpetic pain resolved after treatment with 1 cycle of subcutaneous recombinant interleukin-2.
The first step of leukocyte extravasation, leukocyte rolling, is mediated by E-, P-, and L-selectins. Mice deficient for alpha-1,3-fucosyltransferase VII (FucTVII)(-/-) are characterized by ...deficiency of E-, P-, and L-selectin ligand activity. This model system was used to evaluate the role of the interactions of selectins with their ligands in T and B cell responses. In the present study, FucTVII(-/-) mice showed reduced CD4+ T cell-mediated contact hypersensitivity reactions of the ears to FITC as well as reduced CD8+ T cell-mediated delayed-type hypersensitivity reactions of the footpads against lymphocytic choriomeningitis virus infection. As Langerhans cell migration to local lymph nodes as well as CD4+ and CD8+ T cell induction were found to be normal, the afferent arm of these reactions was not impaired. The reduced inflammatory reactions of the skin were due to inefficient lymphocyte extravasation into the skin. In contrast, extravasation of CD4+ and CD8+ T cells into visceral organs, such as the ovaries or the brain, was not impaired in FucTVII(-/-) mice. Elimination of vaccinia virus and of lymphocytic choriomeningitis virus from ovaries and brain, as well as elimination of tumor cells from several visceral organs was normal. Thus, interactions of selectins with their ligands are important for lymphocyte homing into the skin, but not for lymphocyte extravasation into visceral organs.
Since antigen-persistence plays a role for induction of immunity, we investigated the in vivo pharmacokinetic of a naked DNA vaccine at the site of its action, i.e., in the lymph node. After direct ...intralymphatic injection, naked DNA vaccine degraded within a few hours. In correlation with the short persistence of the DNA vaccine we found that the frequency of vaccination critically influenced the strength of the immune response. In mice vaccinated every 3 days, cytotoxic T-cell responses were enhanced compared to immunization in 6 or 9 days intervals. The results suggest that the so far disappointing efficiency of naked DNA vaccines in humans may be overcome by more frequent vaccination.
: DNA coding for murine interleukin 12 (IL‐12) prevents the formation of B16‐melanoma metastasis when administered intramuscularly. Here, the antitumor effect of IL‐12‐encoding DNA on established ...mouse B16 melanoma and human melanoma tumors was investigated in vivo using two animal models: B16 melanoma in C57B/6 mice and human melanoma in nude mice. In B16 melanoma, intratumoral injections of IL‐12‐encoding DNA resulted in highly significant growth retardation when compared with mice injected with control vector. In the case of the human melanoma model, treatment with DNA coding for IL‐12 induced regression of tumors in all cases, with complete disappearance of the tumor in two out of five animals. DNA treatment did not induce systemic side‐effects. In the animals injected with control vector the human melanoma tumors grew expansively. The therapeutic effect of the DNA injection was mediated in part by natural killer (NK) cells as shown by NK‐depletion experiments. An antivascular effect of IL‐12 treatment was evident in histological examination with endothelial thickening and abrupt changes in vessel diameters. These results suggest that intratumoral plasmid DNA coding for IL‐12 holds some promise as a new therapeutic tool for accessible melanoma lesions and should be tested in clinical trial.
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Spätfolgen nach Immuntherapie Duong, Sophie L.; Zierold, Sarah; Kramer, Rafaela ...
Der Onkologe,
08/2021, Letnik:
27, Številka:
8
Journal Article
Zusammenfassung
Hintergrund
Immuncheckpointinhibitoren (ICI) sind bei zahlreichen Tumorentitäten wirksam, können allerdings immunvermittelte Nebenwirkungen in allen Organsystemen induzieren und so zu ...langfristigen Schäden und Todesfällen führen. Hierbei können Nebenwirkungen auch Monate nach Beendigung der Therapie auftreten und Spätfolgen Jahre nach Beendigung der Therapie bestehen bleiben. Aufgrund des zunehmenden Einsatzes von ICI auch in früheren Tumorstadien müssen diese langfristigen Auswirkungen in die Nutzen-Risiko-Bewertung miteinbezogen werden.
Ziel der Arbeit
Es wird eine Übersicht über die Spätfolgen einer ICI-Therapie gegeben sowie die Datenbasis in Form des internationalen Side Effect Registry Immuno-Oncology (SERIO) zur Dokumentation und Auswertung der immunvermittelten Nebenwirkungen vorgestellt.
Methode
Neben der Auswertung des SERIO-Registers erfolgte eine selektive Literaturrecherche in den Datenbanken PubMed, Cochrane Central Register of Controlled Trials und Google Scholar.
Ergebnisse
Die häufigsten immunvermittelten Nebenwirkungen mit langfristigen Folgen sind kutan (Leukotrichie und melanomassoziierte Hypopigmentierung) und endokrin (Thyreoiditis, Hypophysitis, Adrenalitis, Diabetes). Während Erstere v. a. als stigmatisierend erlebt werden, wird bei den endokrinen Nebenwirkungen meist eine lebenslange Hormonsubstitution notwendig. Neurologische und kardiologische immunvermittelte Nebenwirkungen sind zwar selten, jedoch mit hoher Morbidität und Mortalität assoziiert.
Schlussfolgerungen
Bisher sind prospektive Daten zu langfristigen Auswirkungen von immunvermittelten Nebenwirkungen nicht verfügbar. Das SERIO-Register bietet die Möglichkeit, klinische Fälle systematisch zu sammeln, um ICI-assoziierte Nebenwirkungen besser zu charakterisieren und nachzuverfolgen.
Early detection of melanoma, a potentially lethal type of skin cancer with high prevalence worldwide, improves patient prognosis. In retrospective studies, artificial intelligence (AI) has proven to ...be helpful for enhancing melanoma detection. However, there are few prospective studies confirming these promising results. Existing studies are limited by low sample sizes, too homogenous datasets, or lack of inclusion of rare melanoma subtypes, preventing a fair and thorough evaluation of AI and its generalizability, a crucial aspect for its application in the clinical setting. Therefore, we assessed 'All Data are Ext' (ADAE), an established open-source ensemble algorithm for detecting melanomas, by comparing its diagnostic accuracy to that of dermatologists on a prospectively collected, external, heterogeneous test set comprising eight distinct hospitals, four different camera setups, rare melanoma subtypes, and special anatomical sites. We advanced the algorithm with real test-time augmentation (R-TTA, i.e. providing real photographs of lesions taken from multiple angles and averaging the predictions), and evaluated its generalization capabilities. Overall, the AI showed higher balanced accuracy than dermatologists (0.798, 95% confidence interval (CI) 0.779-0.814 vs. 0.781, 95% CI 0.760-0.802; p<0.001), obtaining a higher sensitivity (0.921, 95% CI 0.900- 0.942 vs. 0.734, 95% CI 0.701-0.770; p<0.001) at the cost of a lower specificity (0.673, 95% CI 0.641-0.702 vs. 0.828, 95% CI 0.804-0.852; p<0.001). As the algorithm exhibited a significant performance advantage on our heterogeneous dataset exclusively comprising melanoma-suspicious lesions, AI may offer the potential to support dermatologists particularly in diagnosing challenging cases.
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