Increased Infiltration of CD8+ T Cells by Dacarbazine in a Patient with Mucosal Penile Melanoma Refractory to Nivolumab
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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.
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.
참고문헌 (8)
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