Recent clinical trials have demonstrated the efficacy of immune checkpoint inhibitors (ICIs) for treating melanoma. However, these previous studies comprised mainly Caucasian populations, in which cutaneous melanoma (CM) is the major clinical type. In contrast, Asian populations have a distinct profile of melanoma and show much higher frequencies of acral lentiginous melanoma (ALM) and mucosal melanoma (MCM). Compared with CM, ALM and MCM show poorer response to ICIs, but the mechanisms have not been fully understood. To evaluate the immune status in each melanoma subtype, we examined the number of total tumor-infiltrating lymphocytes (TILs), CD4+ TILs, CD8+ TILs, and tumor-infiltrating FoxP3+ regulatory T cells (Tregs) to evaluate the immune status in each melanoma subtype using data from 137 patients with melanoma. Total TIL numbers in ALM and MCM were significantly lower than that in CM. CD4+ TIL number in MCM was also lower than CM although CD4+ TIL number in ALM was comparable with CM. In contrast, CD8+ TIL numbers in both ALM and MCM were significantly lower than that in CM. Although number of tumor-infiltrating Tregs was comparable among the 3 subtypes, the proportion of tumor-infiltrating Tregs in CD4+ T cells in MCM was significantly higher than in CM and ALM. Multivariate regression analysis revealed that ALM and MCM were significantly associated with a lower total TIL number, but only MCM was significantly associated with a lower CD4+ TIL number. Multivariate regression analysis also revealed that both ALM and MCM were significantly associated with a lower CD8+ TIL number. Our results suggest that both ALM and MCM are independent factors of lower total TIL number, which may be associated with poorer responses to ICIs in ALM and MCM.

No abstract

The exact mechanisms of the imiquimod (IMQ)-induced antitumor effect have not been fully understood. Although both topical IMQ treatment and anti-PD-1 antibody may be used for primary skin lesions or skin metastases of various cancers, the efficacy of each monotherapy for these lesions is insufficient. Using a murine tumor model and human samples, we aimed to elucidate the detailed mechanisms of the IMQ-induced antitumor effect and analyzed the antitumor effect of combination therapy of topical IMQ plus anti-PD-1 antibody. Topical IMQ significantly suppressed the tumor growth of MC38 in wildtype mice. IMQ upregulated interferon γ (IFN-γ) expression in CD8+ T cells in both the lymph nodes and the tumor, and the antitumor effect was abolished in both Rag1-deficient mice and IFN-γ-deficient mice, indicating that IFN-γ produced by CD8+ T cells play a crucial role in the IMQ-induced antitumor effect. IMQ also upregulated PD-1 expression in T cells as well as PD-L1/PD-L2 expression in myeloid cells, suggesting that IMQ induces not only T-cell activation but also T-cell exhaustion by enhanced PD-1 inhibitory signaling. Combination therapy of topical IMQ plus anti-PD-1 antibody exerted a significantly potent antitumor effect when compared with each single therapy, indicating that the combination therapy is a promising therapy for the skin lesions of various cancers.

Dear Editor, Tufted angioma (TA) is a benign progressive hemangioma that frequently occurs in the trunk. Although the head and neck can also be involved, TA arising in the finger is extremely rare. Here, we report a case of TA arising in the finger as a nodule.A 14-year-old boy presented with a red nodule in the left ring finger that had first appeared approximately 6 months previously and had gradually increased in size. When touched, the lesion caused pain and discomfort. The physical examination showed a 5 mm 9 9 mm, reddish, mildly protruding, tender nodule ( Fig. 1a). Dermoscopy revealed numerous tiny red lacunae separated by thin, whitish linear septa (Fig. 1b). The nodule was excised, and the histopathological sections demonstrated discrete, well-circumscribed aggregates with capillaries and surrounding fibrous tissue throughout the dermis, which was consistent with a cannon-ball appearance (Fig. 1c). These aggregates were composed of rounded, plump endothelial cells as well as small vessels and were adjacent to crescent-shaped vessels (Fig. 1d). Immunohistochemical staining revealed that the capillary aggregates were positive for CD31 and smooth muscle actin despite being negative for desmin and D2-40. On the basis of these findings, TA was diagnosed.

No abstract