Cancer immunotherapy has proven high efficacy in treating diverse cancer entities by immune checkpoint modulation and adoptive T-cell transfer. However, patterns of treatment response differ substantially from conventional therapies, and reliable surrogate markers are missing for early detection of responders versus non-responders. Current imaging techniques using 18F-fluorodeoxyglucose-positron-emmission-tomograpy (18F-FDG-PET) cannot discriminate, at early treatment times, between tumor progression and inflammation. Therefore, direct imaging of T cells at the tumor site represents a highly attractive tool to evaluate effective tumor rejection or evasion. Moreover, such markers may be suitable for theranostic imaging.Methods: We mainly investigated the potential of two novel pan T-cell markers, CD2 and CD7, for T-cell tracking by immuno-PET imaging. Respective antibody- and F(ab´)2 fragment-based tracers were produced and characterized, focusing on functional in vitro and in vivo T-cell analyses to exclude any impact of T-cell targeting on cell survival and antitumor efficacy.Results: T cells incubated with anti-CD2 and anti-CD7 F(ab´)2 showed no major modulation of functionality in vitro, and PET imaging provided a distinct and strong signal at the tumor site using the respective zirconium-89-labeled radiotracers. However, while T-cell tracking by anti-CD7 F(ab´)2 had no long-term impact on T-cell functionality in vivo, anti-CD2 F(ab´)2 caused severe T-cell depletion and failure of tumor rejection.Conclusion: This study stresses the importance of extended functional T-cell assays for T-cell tracer development in cancer immunotherapy imaging and proposes CD7 as a highly suitable target for T-cell immuno-PET imaging.
Immune-checkpoint inhibitors and further immunotherapeutic treatment strategies have significantly extended therapy options for melanoma and other skin cancer entities over the last decade. In the context of a broader application of immunotherapeutic approaches, sufficient ways to monitor the course of the disease during therapy are required. Immunotherapies are based on different ways of modulating the immune system. This leads to complex clinical response patterns including pseudoprogression and others, requiring an adaptation of conventional diagnostic imaging tools or the introduction of novel technologies. In this review, current non-invasive imaging approaches for response assessment during immunotherapies in skin cancers as well as their limitations are discussed. To overcome present hurdles, promising alternatives to better address novel imaging features during immunotherapy are depicted giving an outlook on what can be expected in the future.
The introduction of immune checkpoint inhibitors and targeted therapies has revolutionized melanoma treatment. The downside are immune-mediated adverse events which are frequent and require close patient management. We report a case of severe immune-mediated hepatitis and pneumonitis under combined immune-checkpoint inhibitor therapy requiring immunosuppressive therapy. Under immunosuppressive therapy, however, a series of opportunistic infections occurred. It can be challenging to distinguish the signs of immune-mediated adverse events of checkpoint inhibitors and pathogen-mediated inflammation due to overlaps in clinical and laboratory findings. This case has the goal to rise awareness for infectious complications during immunosuppressive therapy needed to address immune-mediated adverse events of checkpoint inhibitors.
K E Y W O R D Simmune-checkpoint inhibition, immune-related adverse events, pneumonia, pneumonitis
ZusammenfassungImmuncheckpoint‐Inhibitoren und weitere immuntherapeutische Behandlungsansätze haben die Therapieoptionen beim Melanom und anderen Hauttumoren im letzten Jahrzehnt erheblich erweitert. Die breite Anwendung von Immuntherapien erfordert geeignete Methoden zur Überwachung des Krankheitsverlaufs während der Therapie. Immuntherapien beruhen auf einer gezielten Modulation des Immunsystems. Diese führt zu komplexen klinischen Reaktionsmustern wie der Pseudoprogression, die eine Anpassung der konventionellen diagnostischen Bildgebungsmethoden oder die Einführung neuer Technologien erfordern. In dieser Übersichtsarbeit werden die derzeit verfügbaren nichtinvasiven bildgebenden Verfahren zur Beurteilung des Ansprechens auf Immuntherapien bei Hauttumoren mit Vor‐ und Nachteilen dargestellt. Außerdem werden vielversprechende zukünftige Alternativen aufgezeigt, die die neuartigen Anforderungen bei Immuntherapien besonders berücksichtigen sollen.
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