Variable indoleamine 2,3-dioxygenase expression in acral/mucosal melanoma and its possible link to immunotherapy

Immune checkpoint inhibitors have improved the prognosis of advanced melanoma. Although anti-programmed death ligand-1 (PD-L1) is a well-studied biomarker for response to anti-programmed death-1 PD-1 therapy in melanoma, its clinical relevance remains unclear. It has been established that the high expression of indoleamine 2,3-dioxygenase (IDO) is correlated to a response to anti-CTLA-4 treatment in melanoma. However, it is still unknown whether the IDO expression is associated with response to anti-PD-1 therapy in advanced melanoma. In addition, acral and mucosal melanomas, which comprise a great proportion of all melanomas in Asians, are genetically different subtypes from cutaneous melanomas; however, they have not been independently analyzed due to their low frequency in Western countries. To evaluate the association of IDO and PD-L1 expression with response to anti-PD-1 antibody in acral and mucosal melanoma patients, we analyzed 32 Japanese patients with acral and mucosal melanomas treated with anti-PD-1 antibody from the perspective of IDO and PD-L1 expression levels by immunohistochemistry (IHC). Multivariate Cox regression models showed that the low expression of IDO in tumors was associated with poor progression-free survival (HR = 0.33, 95% CI = 0.13-0.81, P = 0.016), whereas PD-L1 expression on tumors was not associated with progression-free survival. Significantly lower expression of IDO in tumors was found in non-responders compared to responders. Assessment of the IDO expression could be useful for the identification of suitable candidates for anti-PD-1 therapy among acral and mucosal melanomas patients. Further validation study is needed to estimate the clinical utility of our findings.