Enhanced IL-34 expression in Nivolumab-resistant metastatic melanoma

Our plain-English summary of Enhanced IL-34 expression in Nivolumab-resistant metastatic melanoma, by N. Han, M. Baghdadi, K. Ishikawa, et al (Inflammation and Regeneration, 2018).

The study

• Authors: N. Han, M. Baghdadi, K. Ishikawa, H. Endo, T. Kobayashi, H. Wada, K. Imafuku, H. Hata, K.I. Seino
• Journal: Inflammation and Regeneration
• Published: 2018;38:3
• Type of article: Case report
• Cited by: 36 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: 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.

Case Presentation: 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.

Conclusion: 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.

In plain English

This case report from Hokkaido University, Japan, is about melanoma, a skin cancer, not asbestos. Malignant pleural mesothelioma appears only in the background, which describes other studies of a signaling protein called IL-34. The patient, a 74-year-old Japanese woman, was diagnosed in February 2008 with Stage III B melanoma of the left sole. After surgery, one dose of interferon beta and eight doses of dacarbazine, melanoma was found in distant lymph nodes. The patient then received the immunotherapy drug nivolumab in 2015 and 2016. The disease first progressed, then partly responded, but new lymph node metastases appeared on the same thigh. The authors stained tissue from the original tumor and from the new metastases. IL-34 staining was statistically significantly higher in the resistant metastases, and this went along with more CD163-positive immune cells called macrophages. In public Human Protein Atlas data, high IL-34 expression was linked to poorer survival in melanoma (P = 0.038). The authors suggested IL-34 has potential as a prognostic marker and treatment target, and said samples from other patients need study.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: case report (one patient), with laboratory tissue staining and an analysis of public Human Protein Atlas survival data
• Who was studied: one 74-year-old Japanese woman, diagnosed in February 2008 at Hokkaido University Hospital, Sapporo, with Stage III B melanoma from a 5-mm thick pigmented lesion on the sole of the left foot
• Exposure: No asbestos exposure was studied. The exposures were cancer treatments: interferon beta (stopped after the first dose), dacarbazine (8 doses, 2014 to 2015), and nivolumab (2 mg/kg every 3 weeks, 2015 to 2016)
• Main results:
  • On nivolumab, the patient's disease was rated progressive at the 4th dose and a partial response at the 15th dose. Melanoma then spread to other distant lymph nodes on the same thigh, which were sampled in December 2016.
  • IL-34 staining was statistically significantly higher in the nivolumab-resistant metastatic melanoma tissue than in the primary melanoma tissue from the same patient
  • In the same patient, higher IL-34 in the refractory metastatic melanoma went along with increased frequencies of CD163-positive macrophages compared with the primary melanoma
  • In a melanoma patient cohort from the Human Protein Atlas (number of patients not given), high IL34 expression was significantly associated with poorer overall survival (P = 0.038)
• The authors' conclusion: The authors suggested that IL-34 may matter in patients with refractory melanoma and has potential as a prognostic biomarker and therapeutic target, which should be evaluated in future work
• Limitations the authors state:
  • The authors stated that in this single case the higher IL-34 could accompany acquired resistance to chemotherapy, acquired resistance to immunotherapy, or a greater degree of malignancy. They said samples from other melanoma patients are needed to clarify this.

Topics

Medical terms in this study, explained in our Lexicon: Nivolumab (Opdivo), Disease Progression, Cytokine, Metastasis, Angiogenesis, Lung Cancer, Pleural Mesothelioma, Immunotherapy.

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