Ann Dermatol.  2016 Aug;28(4):486-490. 10.5021/ad.2016.28.4.486.

Increased Infiltration of CD8⁺ T Cells by Dacarbazine in a Patient with Mucosal Penile Melanoma Refractory to Nivolumab

• Funazumi M
• Namiki T
• Arima Y
• Kato K
• Nojima K
• Tanaka K
• Miura K
• Yokozeki H

• KMID: 2344820
• DOI: http://doi.org/10.5021/ad.2016.28.4.486

Abstract

Primary penile melanomas are rare tumors that represent less than 0.1% of all melanomas. We report a case of a 60-year-old Japanese male with a mucosal penile melanoma and describe an increased CD8⁺ T cell infiltration in brain after dacarbazine (DTIC) administration. After partial penectomy and left inguinal lymphadenectomy, he developed multiple lung, bone, spleen, brain and skin metastases. He was treated with interferon-β, DTIC and nivolumab. However, the metastases were not reduced in size. Immunohistochemistry showed an increase of CD8⁺ T cell infiltration and programmed death-ligand 1 (PD-L1) expression after the administration of DTIC, but the expression of programmed cell death protein 1 (PD-1) was negative. We speculate that DTIC exerted immunostimulatory effects, but nivolumab was ineffective due to the negative expression of PD-1 and/or an insufficient infiltration of CD8⁺ T cells. Although this is only one case, this case report could be the first step to discuss the development of effective therapies against melanoma to take advantage of the increased CD8⁺ T cell infiltration elicited by chemotherapeutic agents. It would be beneficial to pay more attention to the relationship between DTIC and immune checkpoint modulators.

Keyword

CD8; Dacarbazine; Melanoma; Nivolumab; T-lymphocytes

MeSH Terms

Asian Continental Ancestry Group
Brain
Cell Death
Dacarbazine*
Humans
Immunohistochemistry
Lung
Lymph Node Excision
Male
Melanoma*
Middle Aged
Neoplasm Metastasis
Skin
Spleen
T-Lymphocytes*
Dacarbazine

Figure

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  Fig. 1 (A) A pigmented nodule on the urethral orifice (indicated by the white arrow). (B) An atypical melanocytic proliferation arranged in sheets and in nests. (H&E, ×40). (C) Eosinophilic cytoplasm and vesicular pleomorphic nuclei with prominent nucleoli and frequent mitoses (H&E, ×200).

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  Fig. 2 Immunohistochemistry for CD8 in the primary tumor (A), the brain metastatic lesion (D) and a skin metastatic lesion (G). Immunohistochemistry for programmed cell death protein 1 in the primary tumor (B), the brain metastatic lesion (E) and a skin metastatic lesion (H). Immunohistochemistry for programmed death-ligand 1 in the primary tumor (C), the brain metastatic lesion (F) and a skin metastatic lesion (I) (A~I: ×100). Number of cells staining for CD8 expressed as means±standard deviations measured over 10 high-power fields (×400) in the peripheral (J) and inner (K) layer of the tumor. Counting was performed independently by two observers. *p<0.0001.

• 

  Fig. 3 Contrast-enhanced computed tomography for a splenic metastatic lesion (A) before dacarbazine administration, after dacarbazine administration (B), after the first course of nivolumab administration (C), and after the second course of nivolumab administration (D). Diameters of the splenic metastatic lesion (indicated by white arrows) are 13 mm (A), 20 mm (B), 21 mm (C) and 32 mm (D), respectively. Arrows indicate splenic metastatic lesions.

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