Toll-like receptors 7 and 8 expression correlates with the expression of immune biomarkers and positively predicts the clinical outcome of patients with melanoma

Figures & data

Figure 1 Transcriptional levels of TLR7 and TLR8 predict the clinical outcome of patients with melanoma. Survival analysis of melanoma patients (TCGA database) is shown with high and low expressions of TLR7 (A) and TLR8 (B). Survival analysis of melanoma patients (GSE19234) is shown with high and low expressions of TLR7 (C) and TLR8 (D). The patients were divided into two groups based on the median mRNA expression levels of TLR7 and TLR8.

Abbreviations: TLR, Toll-like receptor; TCGA, The Cancer Genome Atlas.

Table 1 Correlation analysis of TLR7/8 and genes of interest

Genes	TLR7			TLR8
	Pearson’s r	95% CI	P-value	Pearson’s r	95% CI	P-value
CCL2	0.5852	0.5225–0.6415	<0.0001	0.6211	0.5624–0.6736	<0.0001
CCL3	0.5302	0.4622–0.5921	<0.0001	0.615	0.5557–0.6682	<0.0001
CCL4	0.6982	0.6488–0.7417	<0.0001	0.8052	0.7710–0.8348	<0.0001
CCL5	0.6795	0.6278–0.7252	<0.0001	0.7656	0.7255–0.8005	<0.0001
CCR2	0.8337	0.8039–0.8592	<0.0001	0.8662	0.8418–0.8871	<0.0001
CCR5	0.8448	0.8169–0.8688	<0.0001	0.904	0.8860–0.9192	<0.0001
CD3E	0.7355	0.6912–0.7744	<0.0001	0.7949	0.7591–0.8258	<0.0001
CD4	0.8087	0.7750–0.8378	<0.0001	0.8267	0.7959–0.8533	<0.0001
CD8A	0.7329	0.6882–0.7720	<0.0001	0.8204	0.7885–0.8478	<0.0001
CD8B	0.7052	0.6568–0.7478	<0.0001	0.7899	0.7534–0.8216	<0.0001
FLT3	0.7221	0.6760–0.7627	<0.0001	0.7331	0.6885–0.7723	<0.0001
FLT3LG	0.5328	0.4649–0.5944	<0.0001	0.5399	0.4727–0.6008	<0.0001
GZMA	0.7354	0.6911–0.7743	<0.0001	0.8283	0.7977–0.8546	<0.0001
GZMB	0.5902	0.5282–0.6460	<0.0001	0.7203	0.6739–0.7610	<0.0001
GZMK	0.7773	0.7390–0.8107	<0.0001	0.8406	0.8120–0.8652	<0.0001
IFNA1	−0.0344	−0.1242 to 0.05591	0.4549	−0.03214	−0.1220 to 0.05821	0.4856
IFNAR1	0.3979	0.3192–0.4712	<0.0001	0.3468	0.2649–0.4237	<0.0001
IFNAR2	0.4473	0.3721–0.5166	<0.0001	0.4728	0.3997–0.5400	<0.0001
IFNB1	0.2058	0.1178–0.2905	<0.0001	0.1833	0.09463–0.2690	<0.0001
IFNG	0.648	0.5925–0.6975	<0.0001	0.7714	0.7321–0.8055	<0.0001
IFNGR1	0.4204	0.3433–0.4920	<0.0001	0.4327	0.3564–0.5032	<0.0001
IRF3	0.03714	−0.05322 to 0.1269	0.4203	0.06945	−0.02086 to 0.1586	0.1315
IRF7	0.2944	0.2098–0.3747	<0.0001	0.2596	0.1735–0.3418	<0.0001
ITGAE	0.3322	0.2495–0.4101	<0.0001	0.3708	0.2904–0.4461	<0.0001
ITGAM	0.7734	0.7344–0.8073	<0.0001	0.7869	0.7500–0.8190	<0.0001
ITGAX	0.5687	0.5044–0.6268	<0.0001	0.6178	0.5587–0.6706	<0.0001
MYD88	0.4415	0.3659–0.5113	<0.0001	0.4432	0.3678–0.5129	<0.0001
PRF1	0.6673	0.6141–0.7145	<0.0001	0.8007	0.7658–0.8309	<0.0001
TLR8	0.8903	0.8700–0.9076	<0.0001

Abbreviations: CI, confidence interval; TLR, Toll-like receptor.

Table 2 Multivariate cox analyses applied to survival model

Parameters	HR	95% CI	P-value
TLR7 (low vs high)	1.982	1.463–2.687	<0.0001
Gender (female vs male)	1.046	0.7598–1.440	0.783
Age	1.026	1.0159–1.037	<0.0001
TNM stage (III and IV vs I and II)	1.671	1.23–2.269	0.001

Abbreviations: HR, hazard ratio; CI, confidence interval; TNM, tumor, node, and metastases; TLR, Toll-like receptor.

Figure 2 Correlation analysis between expressions of TLR7 and factors associated with dendritic cells (DC). Correlation analysis between (A) TLR7 and ITGAM, (B) TLR7 and ITGAX, (C) TLR7 and IFNB, and (D) TLR7 and IRF3.

Note: r, Pearson’s correlation coefficient.
Abbreviations: TLR, Toll-like receptor; IRF3, interferon regulatory factor 3; IFNB, interferon B.

Figure 3 Correlation analysis between expressions of TLR7 and chemokines and their receptors. Correlation analysis between (A) TLR7 and CCR2, (B) TLR7 and CCR5, (C) TLR7 and CCL2, and (D) TLR7 and CCL5.

Note: r, Pearson’s correlation coefficient.
Abbreviation: TLR, Toll-like receptor.

Figure 4 Correlation analysis between expression levels of TLR7 and CD8⁺ cytotoxic T-cell markers. Correlation analysis between (A) TLR7 and CD8A, (B) TLR7 and IFNG, (C) TLR7 and GZMB, and (D) TLR7 and PRF1.

Note: r, Pearson’s correlation coefficient.
Abbreviations: TLR, Toll-like receptor; IFNG, interferon gamma.