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. 2019 Apr 8;120(9):903–912. doi: 10.1038/s41416-019-0444-3

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© Cancer Research UK 2019

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Fig. 5 — Correlation of interleukin (IL)-35 and Arginase-1 (Arg1) in the tumoural (TU) region of non-small cell lung cancer (NSCLC) patients. a Quantitative real-time PCR (qPCR)-based analysis of TNFA mRNA expression in human lung tissue samples from the TU, peritumoural (PT), and control (CTR) region of patients suffering from adenocarcinoma (ADC) (ADC_CTR = 11, ADC_PT = 10, ADC_TU = 13) or squamous cell carcinoma (SCC) (SCC_CTR = 7, SCC_PT = 7, SCC_TU = 9) collectively grouped as NSCLC. b–d Correlation between TNFA/HPRT mRNA level and IL-35⁺ cells per area unit detected via immunohistochemistry (IHC) in the CTR lung tissue of ADC (b, ADC_CTR = 2) and SCC (c, SCC_CTR = 7) subtypes collectively grouped as NSCLC (d, NSCLC_CTR = 9) lung cancer. e–g Correlation between TNFA/HPRT mRNA level and IL-35⁺ cells per area unit detected via IHC in the TU lung tissue of ADC (e, ADC_TU = 6) and SCC (f, SCC_TU = 7) subtypes collectively grouped as NSCLC (g, NSCLC_TU = 13) lung cancer. h qPCR-based analysis of ARG1 mRNA expression in human lung tissue samples from the TU, PT, and CTR region of patients suffering from ADC (ADC_CTR = 25, ADC_PT = 16, ADC_TU = 24) or SCC (SCC_CTR = 19, SCC_PT = 14, SCC_TU = 17) collectively grouped as NSCLC. i–k Correlation between ARG1/HPRT mRNA level and IL-35⁺ cells per area unit detected via IHC in the CTR lung tissue of ADC (i, ADC_CTR = 3) and SCC (j, SCC_CTR = 4) subtypes collectively grouped as NSCLC (k, NSCLC_CTR = 7) lung cancer. l–n Correlation between ARG1/HPRT mRNA level and IL-35⁺ cells per area unit detected via IHC in the TU lung tissue of ADC (l, ADC_TU = 6) and SCC (m, SCC_TU = 6) subtypes collectively grouped as NSCLC (n, NSCLC_TU = 12) lung cancer. o The immunosuppressive role of IL-35 in NSCLC: in the solid tumour, Arg1⁺ M2 macrophages attract IL-35-producing inducible Treg cells (iTr35), which support lung tumour growth. In the control region, a new macrophage subtype seems to secrete IL-35, which further promotes an immunosuppressive environment and supports the development of NSCLC. Data are presented as mean ± SEM and significance levels are indicated as follows: *p < 0.05, **p < 0.01, ***p < 0.001