Enhanced IL-34 expression in Nivolumab-resistant metastatic melanoma

Immunotherapies that target immune-checkpoint molecules such PD-1 have helped to achieve durable responses in melanoma treatment. However, 25% of melanoma patients who showed objective responses to PD-1 blockade develop resistance and suffer from disease progression and ultimately death, which neces...

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Bibliographic Details
Published in:Inflammation and Regeneration 2018-03, Vol.38 (1), p.3-5
Main Authors: Han, Nanumi, Baghdadi, Muhammad, Ishikawa, Kozo, Endo, Hiraku, Kobayashi, Takuto, Wada, Haruka, Imafuku, Keisuke, Hata, Hiroo, Seino, Ken-Ichiro
Format: Article
Language:English
Subjects:
Antibodies
Antigens
Biomarkers
Cancer therapies
Case Report
Chemotherapy
Cytokines
Disease
Immunotherapy
Insulin-like growth factors
Interleukin-34
Lung cancer
Lymphatic system
Medical prognosis
Medical research
Melanoma
Metastasis
Patients
Physiology
Skin cancer
Tumor-associated macrophage
Tumors
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Summary:Immunotherapies that target immune-checkpoint molecules such PD-1 have helped to achieve durable responses in melanoma treatment. However, 25% of melanoma patients who showed objective responses to PD-1 blockade develop resistance and suffer from disease progression and ultimately death, which necessitates the identification of related resistance mechanisms.IL-34 is a cytokine that controls the biology of myeloid cell lineage through binding to CSF-1R. IL-34 is importantly involved in the pathogenesis of various diseases. In cancer, the expression of IL-34 has been suggested to associate with tumor growth, metastasis, angiogenesis, and therapeutic resistance such as in lung cancers and malignant pleural mesotheliomas. In this study, we evaluate the possible involvement of IL-34 in immunotherapeutic resistance. Melanoma resection species were obtained from a patient who developed a refractory melanoma against immunotherapy with Nivolumab, and stained with anti-IL-34, anti-melanoma antigens and anti-CD163 antibody. Staining of these markers was compared between primary or metastatic refractory melanoma tissues. Immunohistochemistry staining of melanoma tissues showed an enhanced expression of IL-34 in metastatic refractory melanoma compared to primary melanoma tissues, which correlates with increased frequencies of CD163 macrophages. We introduce for the first time a clinical case of a patient with metastatic refractory melanoma that acquired resistance to anti-PD-1 immunotherapy, showing an enhanced expression of IL-34 in refractory melanoma tissues.
ISSN:1880-9693
1880-8190
DOI:10.1186/s41232-018-0060-2