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Inter‐ and intrapatient heterogeneity of indoleamine 2,3‐dioxygenase expression in primary and metastatic melanoma cells and the tumour microenvironment
Author(s) -
Gide Tuba N,
Allanson Benjamin M,
Menzies Alexander M,
Ferguson Peter M,
Madore Jason,
Saw Robyn P M,
Thompson John F,
Long Georgina V,
Wilmott James S,
Scolyer Richard A
Publication year - 2019
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/his.13814
Subject(s) - melanoma , medicine , indoleamine 2,3 dioxygenase , immunohistochemistry , immunotherapy , biomarker , pathology , cancer research , oncology , immune system , immunology , biology , tryptophan , biochemistry , amino acid
Aims Indoleamine 2,3‐dioxygenase ( IDO ), an immunomodulatory enzyme, facilitates immune escape by tumours and promotes tumour progression. IDO inhibitors with and without additional anti‐ PD ‐1 therapy have been evaluated in recent and ongoing melanoma clinical trials, but IDO expression in melanoma tumours, and therefore its potential role as a predictive biomarker remains unknown. This study sought to evaluate IDO expression in immunotherapy‐naive metastatic melanoma patients in order to determine patterns of expression in corresponding primary melanomas, locoregional metastases and distant metastases. Methods and results Here, we evaluated IDO expression using immunohistochemistry in 99 melanoma tumour samples from 43 immunotherapy‐naive patients with metastatic melanoma to determine patterns of expression in primary melanomas ( n = 29), locoregional metastases ( n = 36) and distant metastases ( n = 34). Thirty‐seven per cent of patients demonstrated tumour IDO expression in at least one specimen. Twelve of 35 patients (34%) with longitudinal specimens (i.e. two or more separate specimens from different disease stages in the same patient) displayed heterogeneous IDO staining between samples. Tumour IDO expression positively correlated with tumour‐infiltrating lymphocyte ( TIL ) score as well as the number of IDO ‐expressing mononuclear cells in the primary melanoma ( P < 0.0001 and P = 0.0011, respectively) and nodal metastases ( P = 0.049 and P = 0.037, respectively), but not in distant metastases. Furthermore, tumour IDO expression correlated positively with PD ‐L1 expression by melanoma cells among all specimens ( P = 0.0073). Conclusions Therefore, while assessment of tumour IDO expression warrants evaluation in melanoma patient cohorts treated with IDO inhibitors dosed at levels proven to inhibit the target by pharmacodynamic assessment, its utility as a biomarker may be limited by intertumoral heterogeneity.