Mechanisms of checkpoint inhibition-induced adverse events

Urwyler, Pascal; Earnshaw, Irina; Bermudez, Maria; Perucha, Esperanza; Wu, Weiju; Ryan, Sarah; McDonald, Louisa; Karagiannis, Sophia N.; Taams, Leonie S.; Powell, Nick; Cope, Andrew; Papa, Sophie

doi:10.1111/cei.13421

Cited by 43 publications

(35 citation statements)

References 101 publications

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“…Ein anderer Ansatz beinhaltete die Kombination von PD-L1-CD80-Heterodimerisierung und Suppression der CTLA-4/CD80-Achse [17]. Gegenwärtig werden die Antikörper Ipilimumab und Tremelimumab gegen CTLA-4 eingesetzt, während Nivolumab, Pembrolizumab und Cemiplimab für das Targeting von PD-1 und Atezolizumab und Avelumab gegen PD-L1 zur Anwendung kommen [14, 18, 19].…”

Section: Einführungunclassified

Moderne Aspekte der Immuntherapie mit Checkpoint-Inhibitoren bei Melanom

et al. 2020

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Das Melanom gehört zu den am stärksten immunogenen Tumoren. Dennoch ist es in der Lage, sich einer antitumoralen Immunantwort zu entziehen, indem es Toleranzmechanismen, einschließlich negativer Immuncheckpoint-Moleküle, nutzt. Die am umfassendsten untersuchten Immuncheckpoints sind CTLA-4 (cytotoxic T lymphocyte-associated protein-4) und PD-1 (programmed cell death protein 1). Immuncheckpoint-Inhibitoren (ICI), die in den vergangenen 10 Jahren häufig zur Behandlung von Melanomen eingesetzt wurden, können antitumorale Immunreaktionen auslösen und eine Rückbildung des Melanoms bewirken. Patienten, die auf die ICI-Behandlung ansprachen, erreichten eine langanhaltende Remission oder einen Zustand der Krankheitskontrolle. Eine große Gruppe von Patienten sprach dagegen nicht auf diese Therapie an, was darauf hindeutet, dass es zu einer Entwick

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Section: Einführungunclassified

Moderne Aspekte der Immuntherapie mit Checkpoint-Inhibitoren bei Melanom

et al. 2020

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“…The mechanisms of action of immunotherapy are focused on specific targets of the counter-regulatory mechanisms of the immune response [4][5][6][7][8]. However, immunotherapy is also associated with immune-related adverse events(irAEs) that represent tissue-specific dysimmune inflammatory responses [9][10][11][12][13][14].…”

Section: Introductionmentioning

confidence: 99%

Immunotherapy in the Treatment of Metastatic Melanoma: Current Knowledge and Future Directions

Ralli

Botticelli

Visconti

et al. 2020

Journal of Immunology Research

164

138

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Melanoma is one of the most immunologic malignancies based on its higher prevalence in immune-compromised patients, the evidence of brisk lymphocytic infiltrates in both primary tumors and metastases, the documented recognition of melanoma antigens by tumor-infiltrating T lymphocytes and, most important, evidence that melanoma responds to immunotherapy. The use of immunotherapy in the treatment of metastatic melanoma is a relatively late discovery for this malignancy. Recent studies have shown a significantly higher success rate with combination of immunotherapy and chemotherapy, radiotherapy, or targeted molecular therapy. Immunotherapy is associated to a panel of dysimmune toxicities called immune-related adverse events that can affect one or more organs and may limit its use. Future directions in the treatment of metastatic melanoma include immunotherapy with anti-PD1 antibodies or targeted therapy with BRAF and MEK inhibitors.

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“…Despite the initial hype, due to promising results, playing with the immune system raised important issues in many treated patients together with controversial results. Indeed, the removal of the intrinsic immune suppression can trigger a cascade of events with serious adverse effects [2].…”

Section: Introductionmentioning

confidence: 99%

Relevance of immune cell and tumor microenvironment imaging in the new era of immunotherapy

Galli

Aguilera

Palermo

et al. 2020

J Exp Clin Cancer Res

206

139

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Tumor-infiltrating immune cells play a key role against cancer. However, malignant cells are able to evade the immune response and establish a very complex balance in which different immune subtypes may drive tumor progression, metastatization and resistance to therapy. New immunotherapeutic approaches aim at restoring the natural balance and increase immune response against cancer by different mechanisms. The complexity of these interactions and the heterogeneity of immune cell subpopulations are a real challenge when trying to develop new immunotherapeutics and evaluate or predict their efficacy in vivo. To this purpose, molecular imaging can offer non-invasive diagnostic tools like radiopharmaceuticals, contrast agents or fluorescent dyes. These agents can be useful for preclinical and clinical purposes and can overcome [ 18 F]FDG limitations in discriminating between trueprogression and pseudo-progression. This review provides a comprehensive overview of immune cells involved in microenvironment, available immunotherapies and imaging agents to highlight the importance of new therapeutic biomarkers and their in vivo evaluation to improve the management of cancer patients.

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Mechanisms of checkpoint inhibition-induced adverse events

Cited by 43 publications

References 101 publications

Moderne Aspekte der Immuntherapie mit Checkpoint-Inhibitoren bei Melanom

Moderne Aspekte der Immuntherapie mit Checkpoint-Inhibitoren bei Melanom

Immunotherapy in the Treatment of Metastatic Melanoma: Current Knowledge and Future Directions

Relevance of immune cell and tumor microenvironment imaging in the new era of immunotherapy

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