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

Abstract

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.

• Authors: Natsuko Iga, Atsushi Otsuka, Masahiro Hirata, Tatsuki R Kataoka, Hiroyuki Irie, Chisa Nakashima, Shigeto Matsushita, Hiroshi Uchi, Yuki Yamamoto, Takeru Funakoshi, Yasuhiro Fujisawa, Koji Yoshino, Taku Fujimura, Hiroo Hata, Yoshihiro Ishida, Kenji Kabashima
• Journal: Cancer science (Cancer Sci) Vol. 110 Issue 11 Pg. 3434-3441 (Nov 2019) ISSN: 1349-7006 [Electronic] England
• PMID: 31509303 (Publication Type: Journal Article)
• Copyright: © 2019 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Chemical References

• CTLA-4 Antigen
• CTLA4 protein, human
• Indoleamine-Pyrrole 2,3,-Dioxygenase
• Programmed Cell Death 1 Receptor
• BRAF protein, human
• Proto-Oncogene Proteins B-raf

Topics

• Aged
• Asian People
• CTLA-4 Antigen (antagonists & inhibitors)
• Female
• Humans
• Immunotherapy
• Indoleamine-Pyrrole 2,3,-Dioxygenase (metabolism)
• Japan
• Kaplan-Meier Estimate
• Male
• Melanoma (enzymology, mortality, pathology, therapy)
• Middle Aged
• Mutation
• Programmed Cell Death 1 Receptor (metabolism)
• Progression-Free Survival
• Proportional Hazards Models
• Proto-Oncogene Proteins B-raf (genetics)
• Skin Neoplasms (enzymology, mortality, pathology, therapy)