Immune Checkpoint Blockade and Skin Toxicity Pathogenesis

Ma, Barbara; Anandasabapathy, Niroshana

doi:10.1016/j.jid.2021.06.040

Cited by 15 publications

(15 citation statements)

References 98 publications

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“…As described above, ICIs such as anti-PD1 Abs and anti-CTLA4 Abs have become anchor drugs in the treatment of advanced melanoma [ 1 , 2 , 5 ] ( Table 1 ). ICIs significantly prolong survival in patients with metastatic melanoma [ 1 , 2 , 13 ], but the associated risk of irAEs is an important consideration [ 46 , 47 , 48 ]. Among such irAEs, dermatological toxicities are among the most common, well-known and earliest onset irAEs [ 46 , 47 , 48 ]; however, especially in clinical studies, dermatological toxicities are categorized as “skin eruption”, and they were not further described.…”

Section: Adverse Events Of Icismentioning

confidence: 99%

“…ICIs significantly prolong survival in patients with metastatic melanoma [ 1 , 2 , 13 ], but the associated risk of irAEs is an important consideration [ 46 , 47 , 48 ]. Among such irAEs, dermatological toxicities are among the most common, well-known and earliest onset irAEs [ 46 , 47 , 48 ]; however, especially in clinical studies, dermatological toxicities are categorized as “skin eruption”, and they were not further described. Since cutaneous irAEs could present with various manifestations, and since the treatment for these cutaneous irAEs is different for each phenotype [ 46 , 47 ], the classification of cutaneous irAEs is important for the safe use of ICIs.…”

Section: Adverse Events Of Icismentioning

confidence: 99%

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Immunotherapy for Melanoma: The Significance of Immune Checkpoint Inhibitors for the Treatment of Advanced Melanoma

Fujimura

Muto

Asano

2022

IJMS

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Therapeutic options for treating advanced melanoma have progressed rapidly in recent decades. Until 6 years ago, the regimen for treating advanced melanoma consisted mainly of cytotoxic agents such as dacarbazine and type I interferons. Since 2014, anti-programmed cell death 1 (PD1) antibodies have been recognized as anchor drugs for treating advanced melanoma, with or without additional combination drugs such as ipilimumab, but the efficacies of these immunotherapies are not fully satisfactory. In this review, we describe the development of the currently available anti-PD1 Abs-based immunotherapies for advanced melanoma, focusing on their efficacy and immune-related adverse events (AEs), as well as clinical trials still ongoing for the future treatment of advanced melanoma.

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Section: Adverse Events Of Icismentioning

confidence: 99%

Section: Adverse Events Of Icismentioning

confidence: 99%

Immunotherapy for Melanoma: The Significance of Immune Checkpoint Inhibitors for the Treatment of Advanced Melanoma

Fujimura

Muto

Asano

2022

IJMS

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“…This prevents immune cells from reaching tumour cells and attacking them. [ 164 , 165 , 166 , 167 , 168 , 169 , 170 , 171 , 172 , 173 , 174 , 175 , 176 , 177 , 178 ]. PD-L1 is present in exosomes released from melanoma cells [ 178 , 179 , 180 , 181 , 182 , 183 , 184 , 185 , 186 ]; however, exosomes derived from metastasised melanoma cells have a higher PD-L1 content than those derived from primary focal melanoma cells.…”

Section: Ev-mediated Immune Escape Of Cancer Cellsmentioning

confidence: 99%

“…Melanoma elicits a particularly strong immune response, and multiple immune checkpoint inhibitors have been approved by the US Food and Drug Administration for the treatment of melanoma [ 163 , 164 , 165 , 166 , 167 , 168 , 169 , 170 ]. Interestingly, based on PD-L1 levels in exosomes, patients who are most likely to respond to checkpoint inhibitors can be identified and the response to these drugs can be evaluated [ 162 , 194 , 196 , 197 , 198 , 199 ].…”

Section: Ev-mediated Immune Escape Of Cancer Cellsmentioning

confidence: 99%

Molecular Docking and Intracellular Translocation of Extracellular Vesicles for Efficient Drug Delivery

Matsuzaka

Yashiro

2022

IJMS

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Extracellular vesicles (EVs), including exosomes, mediate intercellular communication by delivering their contents, such as nucleic acids, proteins, and lipids, to distant target cells. EVs play a role in the progression of several diseases. In particular, programmed death-ligand 1 (PD-L1) levels in exosomes are associated with cancer progression. Furthermore, exosomes are being used for new drug-delivery systems by modifying their membrane peptides to promote their intracellular transduction via micropinocytosis. In this review, we aim to show that an efficient drug-delivery system and a useful therapeutic strategy can be established by controlling the molecular docking and intracellular translocation of exosomes. We summarise the mechanisms of molecular docking of exosomes, the biological effects of exosomes transmitted into target cells, and the current state of exosomes as drug delivery systems.

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“…For example, patients with melanoma, who developed vitiligo as irAE after administration of ICI, often enjoyed favorable antimelanoma outcomes 1 . In addition, irAE occurs most quickly and frequently in the skin, 2 often resulting in discontinuing the use of ICI. Skin toxicities as irAE have been reported to occur in more than one‐third of the treated patients, and include pruritus, eczema‐like spongiotic dermatitis, lichenoid reactions, psoriasis, vitiligo, and other autoimmune manifestations such as bullous pemphigoid, alopecia areata, and dermatomyositis 3 …”

Section: Introductionmentioning

confidence: 99%

Loss of epidermal Langerhans cells in psoriasiform lesions of de novo induced or worsened pre‐existing psoriasis following uses of immune checkpoint inhibitors

Kase

Fujita

Ota

et al. 2022

The Journal of Dermatology

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Immune checkpoint inhibitors (ICI), including monoclonal antibodies to programmed death 1, programmed death ligand 1, and cytotoxic T lymphocyte‐associated antigen 4, have provided great therapeutic benefits for cancer patients at advanced stages. However, the introduction of ICI frequently results in the development of immune‐related adverse events (irAE) through activation of autoreactive T cells. Here, we present three cases of cancer patients with cutaneous irAE, including development of de novo psoriasis and exacerbation of pre‐existing psoriasis. Interestingly, these patients shared an altered histological feature characterized by loss of epidermal CD1a+ cells, namely Langerhans cells (LC), in the psoriasiform lesions in contrast to “conventional psoriasis” exhibiting unchanged or activated LC. A possible underlying mechanism was that ICI‐mediated hyperactivation of effector T cells contributed to aggravation or establishment of psoriasis phenotype, which might be associated with direct cytotoxicity or expulsion of LC from the epidermis.

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Immune Checkpoint Blockade and Skin Toxicity Pathogenesis

Cited by 15 publications

References 98 publications

Immunotherapy for Melanoma: The Significance of Immune Checkpoint Inhibitors for the Treatment of Advanced Melanoma

Immunotherapy for Melanoma: The Significance of Immune Checkpoint Inhibitors for the Treatment of Advanced Melanoma

Molecular Docking and Intracellular Translocation of Extracellular Vesicles for Efficient Drug Delivery

Loss of epidermal Langerhans cells in psoriasiform lesions of de novo induced or worsened pre‐existing psoriasis following uses of immune checkpoint inhibitors

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