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

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.

<b>Herbological Study on the Quality and Toxicity of Aconite Root </b> / 日本東洋医学雑誌

The crude drug Aconite Root (<i>bushi </i>in Japanese) contains toxic compounds called bushi diester alkaloids(BDA), and the raw material with high BDA content has been considered suitable for processing into prepared <i>bushi</i>. Moreover, processing methods and an upper BDA content limit are prescribed in the 16th edition of Japanese Pharmacopoeia. In this study, we closely examined descriptions of high quality <i>bushi </i>in ancient herbal literature, and elucidated the relationship between <i>bushi </i>forms and BDA contents. The results showed that large-sized <i>bushi </i>with enlarged rootlets called “horns” (<i>tsuno </i>in Japanese) were considered higher quality, and the horns and the root tops (<i>hozo </i>in Japanese) were cut off when used as <i>bushi</i>. Meanwhile, chemical studies have shown that larger <i>bushi </i>contains less BDA, and the root tops and the horns contain more BDA than the root body. These results suggest that selecting larger roots and cutting off the more potent parts were processes for reducing BDA. Therefore we conclude that consistently less toxic <i>bushi </i>was considered a higher quality product in ancient times.