Pathology of immune-mediated tissue lesions following treatment with immune checkpoint inhibitors

Ibraheim, Hajir; Perucha, Esperanza; Powell, Nick

doi:10.1093/rheumatology/kez465

Cited by 44 publications

(36 citation statements)

References 84 publications

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“…On the other hand, their increasing use has brought to attention numerous immune mediated side effects, little described until now, which can affect virtually any organ system. Some examples include enterocolitis, pneumonitis, hepatitis, hypophysitis, inflammatory arthritis, and a variety of skin manifestations [5]. With respect to the latter, they can further be categorized in four groups according to histological patterns: inflammatory, immunobullous, alteration of epidermal keratinocytes, and alteration of epidermal melanocytes, in which tumoral melanosis is included [5].…”

Section: Case Discussionmentioning

confidence: 99%

Tumoral melanosis after immunotherapy with pembrolizumab - a response sign mimicking melanoma

Relvas

Alves²,

Mariano³

et al. 2020

DOJ

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Section: Case Discussionmentioning

confidence: 99%

Tumoral melanosis after immunotherapy with pembrolizumab - a response sign mimicking melanoma

Relvas

Alves²,

Mariano³

et al. 2020

DOJ

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“…A retrospective study showed that the most common adverse events were colitis, hepatitis, adrenocorticotropic hormone insufficiency, and hypothyroidism, followed by type 1 diabetes, acute kidney injury, and myocarditis [ 64 ]. Skin, rheumatic toxicity and pneumonitis have also been reported [ 65 ].…”

Section: Introductionmentioning

confidence: 99%

Malignant Melanoma of the Gastrointestinal Tract: Symptoms, Diagnosis, and Current Treatment Options

Kohoutová

Worku

Aziz

et al. 2021

Cells

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Malignant melanoma (MM) has become the fifth most frequent cancer in the UK. It is the most common carcinoma to metastasize to the gastrointestinal (GI) tract. MM particularly has an affinity to spread to the small bowel, which is followed by the involvement of the stomach and large intestine. Excellent endoscopic options including video capsule endoscopy and enteroscopy are available for a precise diagnosis of GI involvement by a metastatic MM. The complete surgical resection of GI metastatic MM in carefully selected patients not only provides symptom control, but has also been associated with an increase in overall survival. The approval of BRAF-targeted therapies and immune checkpoint inhibitors has transformed therapeutic approaches for patients with metastatic MM over the past decade. Currently, the overall survival of patients with advanced metastatic MM who have been treated with a combination of immunotherapeutic agents reaches 52% at five years. The role of surgery for patients with the metastatic involvement of the GI tract with MM is evolving in the era of effective systemic treatments.

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“…It is important to mention that higher grade irAEs were observed when anti-PD-1 and anti-CTLA-4 were combined, similarly to patient responses to combination ICI therapy. Altogether, it is likely that the development of irAEs is a multifactorial process leading to patient-specific organ involvement [26].…”

Section: Discussionmentioning

confidence: 99%

A novel mouse model for checkpoint inhibitor-induced adverse events

et al. 2021

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Immune checkpoint inhibitors have demonstrated significant efficacy in the treatment of a variety of cancers, however their therapeutic potential is limited by abstruse immune related adverse events. Currently, no robust animal model exists of checkpoint inhibitor-induced adverse events. Establishing such a model will improve our mechanistic understanding of this process, which in turn will inform design of improved therapies. We developed a mouse model to determine inflammatory toxicities in response to dual checkpoint blockade in the presence of syngeneic tumors. Mice from susceptible genetic backgrounds received intraperitoneal injections of anti-mouse PD-1 and CTLA-4 antibodies. The mice were monitored for weight loss and histologic evidence of inflammation. Blood was collected for basic metabolic panels and titers of anti-nuclear antibodies. In parallel, mice were also treated with prednisolone, which is commonly used to treat immune related adverse events among cancer patients. Among all the genetic backgrounds, B6/lpr mice treated with anti-CTLA-4 and anti-PD-1 antibodies developed more substantial hepatitis, pancreatitis, colitis, and pneumonitis characterized by organ infiltration of immune cells. Mice that developed tissue infiltration demonstrated high serum levels of glucose and high titers of anti-nuclear antibodies. Finally, while administration of prednisolone prevented the development of the inflammatory adverse events, it also abrogated the protective anti-tumor effect of the checkout inhibitors. Genetic background and treatment modalities jointly modified the inflammatory adverse events in tumor bearing mice, suggesting a complex mechanism for checkpoint inhibitor-related inflammation. Future studies will assess additional genetic susceptibility factors and will examine possible contributions from the administration of other anti-inflammatory drugs.

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Pathology of immune-mediated tissue lesions following treatment with immune checkpoint inhibitors

Cited by 44 publications

References 84 publications

Tumoral melanosis after immunotherapy with pembrolizumab - a response sign mimicking melanoma

Tumoral melanosis after immunotherapy with pembrolizumab - a response sign mimicking melanoma

Malignant Melanoma of the Gastrointestinal Tract: Symptoms, Diagnosis, and Current Treatment Options

A novel mouse model for checkpoint inhibitor-induced adverse events

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