TABLE 3.
IDO gene transcription studies in HNSCC
| First author, year (country) | Cases (n), source | Method of analysis | Results interpretation |
|---|---|---|---|
| Economopoulou, 46 2020 (Greece) | 113 locally advanced HNSCC patients who underwent cisplatin chemoradiation, peripheral blood collected at baseline and 1 wk after end of treatment | Expression of IDO1 in the EpCAM+CTC fraction before and after cisplatin chemoradiation. Multivariate Cox regression analysis was used to assess the prognostic value of PD‐L1 and IDO1 expression | IDO1 was significantly overexpressed at baseline compared to post‐treatment (P = .007). IDO1 mRNA expression at baseline was associated with better PFS (HR = 0.19, P = .017). Post‐treatment IDO1 mRNA levels correlated with worse OS (HR = 3.27, P = .008). Patients with combined decreased expression of PD‐L1 and IDO1 post‐treatment had better PFS (P = .043) and OS (P = .021) |
| Sailer, 44 2019 (Germany) | 528 HNSCC patients, TCGA; and 138 HNSCC patients as a validation cohort from the University Hospital Bonn | Methylation of 3 CpG sites was correlated with mRNA expression, immune cell infiltration, mutational burden, HPV status and OS | IDO1 methylation and IDO1 mRNA expression were inversely correlated in the promotor and promoter flank region. IDO1 promoter flank hypermethylation was associated with poor OS (P < .001). These suggest that IDO1 expression levels are epigenetically regulated by DNA methylation |
| Lecerf, 42 2019 (France) | 96 HNSCC patients who underwent primary surgery | Real‐time polymerase chain reaction was used to assess the expression of 46 immune‐related genes | IDO1 (75%) was among the most significantly overexpressed immune‐related genes and had significantly higher mRNA expression level in HNSCC compared to normal head and neck tissue (P < .0001) |
| Chen, 43 2019 (China) | 167 oral SCC gene expression data set (GSE30784) and 54 oral SCC DNA methylation data set (GSE75537), obtained from the GEO | Correlations between methylation level of CpG sites and OS of oral SCC patients were assessed by univariate Cox regression analysis followed by robust likelihood‐based survival analysis | A two‐CpG‐based prognostic signature for OSCC OS prediction was obtained, which included the sites cg17892178 and cg17378966 that are located in NID2 and IDO1, respectively |
| Krishna, 39 2018 (USA) | 119 HNSCC transcriptomes | Epitope mapping from HPV+HNSCC PBMCs using Elispot, flow cytometry immune cell phenotyping, ssGSEA of HPV and immune gene signatures | IDO was strongly expressed in HPV+ vs HPV− HNSCC (P = .001). Its expression correlated with E7 HPV antigen expression (R 2 = 0.84, P = .033). Combined inhibition of PD‐1 and IDO‐1 can sensitise HPV+HNSCCs to CD8+ cytotoxic T‐lymphocyte‐mediated cytotoxicity |
| Page, 82 2018 (USA) | 3D‐EX platform, 3D tumour microspheres were produced from fresh HNSCC | NanoString analysis for expression of genes including IDO1 | Increased expression of IDO1 gene in HNSCC which were responsive to checkpoint inhibitor treatment ex vivo |
| Foy, 40 2017 (France) | 212 oral SCC who were NSND, HPV+samples were excluded. 4 cohorts: TCGA, GEO1, GEO2, CLB | Gene expression profiles generated using microarrays and targeted‐RNA sequencing. Functional pathway analysis performed using ssGSEA and STRING | IDO1 was overexpressed in tumours from NSND vs SD (P = .0046). Elderly female patients were more common in NSND and harboured less gene mutations (P = .0006). PD‐L1 and IDO1 were co‐overexpressed, suggesting a higher potential benefit of combination therapy involving both |
| Saâda‐Bouzid, 47 2017 (France) | 36 recurrent metastatic HNSCC treated with anti‐PD‐1 or anti‐PD‐L1 or in combination with a second checkpoint inhibitor | Extraction of blood DNA and genotyped by MassARRAY and multivariate analysis with PFS and OS | A genotype of IDO1 rs3739319 (A/G or A/A) was associated with a longer PFS and OS, (HR = 8.4, P = .002) and (HR = 6.2, CI95% 1.5‐25.9, P = .01), respectively. Allelic variation of IDO1 rs3739319G>A, implicated in transcription and regulation was associated with longer survival in patients treated with anti‐PD‐1 therapy |
| Wirth, 41 2017 (USA) | Validation cohort of 25 HPV+HNSCC patients | Microarray of 59 immune‐related genes to compare expression profiles in HPV+HNSCCs. qPCR and protein expression assay used in validation cohort | There was a 65‐fold increase in IDO1 in 10 PD‐L1+ vs 5 PD‐L1− HPV+HNSCCs (P = .004). IDO1 expression was upregulated and co‐localised in the TME of the validation cohort. IDO1 expression increased and correlated with disease progression in anti‐PD‐1 treated HNSCC patients |
| Won, 45 2017 (USA) | 15 patients with stage III‐IV HNSCC, blood specimen collected before, during and after RT | Gene expression analysis in patients’ PBMCs | A 3.6‐fold (P = .1) increase seen in IDO expression in patients’ PBMCs during RT along with other protein mediators that promote immune suppression, suggesting RT could induce tolerogenic effects in HNSCC which can be targeted with checkpoint inhibitor therapy |
Abbreviations: HPV, human papillomavirus; PBMCs, peripheral blood mononuclear cells; ssGSEA, single‐sample gene set enrichment analysis; SCC, squamous cell carcinoma; TCGA, The Cancer Genome Atlas; GEO, Gene Expression Omnibus; CLB, Centre Léon Bérard cancer centre, Lyon, France; NSND, never‐smokers and never‐drinkers; SD, smokers drinkers; STRING, search tool for the retrieval of interacting genes/proteins; qPCR, quantitative polymerase chain reaction; PFS, progression‐free survival; OS, overall survival; RT, radiotherapy.