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

Expert Impact

Concepts for which they have has direct influence: Cell death , Programmed cell , 1 pd1 , Dacarbazine dtic , Immune checkpoint , L1 expression , Death ligand .

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Douglas R Green
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Guido Kroemer
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Jun‐Ying Yuan
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Stanley J Korsmeyer
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John C Reed
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Craig B Thompson
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Increased Infiltration of CD8+ T Cells by Dacarbazine in a Patient with Mucosal Penile Melanoma Refractory to Nivolumab

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.