Abstract
BackgroundPattern recognition receptors (PRRs) family plays a vital role in the initial stage of innate immune response and the subsequent activation of adaptive immunity. Increasing evidences have indicated that several PRRs play critical roles in the progress of inflammation and tumorigenesis. However, the comprehensive significance of PRRs family in clinical prognosis of different cancers is still elusive.MethodsWe analyzed expression of 20 canonical PRRs in tumor samples from 9502 patients of 33 tumor types. Next, we used expression profiles of PRRs in skin cutaneous melanoma (SKCM) to build a Cox prognosis model. Then, we analyzed immune infiltration features and immune activity of high risk score and low risk score patients. Finally, we analyzed the single-cell sequencing data of different cancers and detected the expression of PRRs in mouse melanoma model to identify PRRs-expressing cell types.ResultsWe found PRRs had a significantly positive correlation with prognosis in SKCM rather than other tumors, and PRR-based Cox model had a much better prognosis potential than any single PRR. Further analysis shows risk score could indicate immunocyte infiltration and immune activity in SKCM. We also found the expressions of some PRR genes were highly correlated with the expression of immune checkpoints molecules in SKCM, indicating they could be indicators for clinical immune therapy. Finally, we found only in SKCM samples, the expression of PRRs is especially high in a subpopulation of macrophages with a trait of CD206 low expression, probably explaining why PRRs have prognosis potential in melanoma.ConclusionsOur study reveals PRR family in macrophages has a positive prognosis potential in melanoma and could be valuable for clinical prognosis and immune therapy.
Highlights
Pattern recognition receptors (PRRs) family, including Toll-like receptors (TLRs), Nod-like receptors (NLRs), and other types of nucleic acid sensors, play a vital role in the initial stage of innate immune response [1]
We found the expressions of some PRR genes were highly correlated with the expression of immune checkpoints molecules in skin cutaneous melanoma (SKCM), indicating they could be indicators for clinical immune therapy
PRRs can promote the formation of cancer, for example, alveolar epithelial TLR3 can be activated by tumor exosomal RNAs to promote formation of lung pro-metastatic niche [4]; nuclear cyclic GMP-AMP synthase can suppress DNA repair and promote tumorigenesis [5]; upregulation of TLR2 induced by signal transducer and activator of transcription 3 (STAT3) can promote gastric tumorigenesis that independent of tumor inflammation [6]
Summary
Pattern recognition receptors (PRRs) family, including Toll-like receptors (TLRs), Nod-like receptors (NLRs), and other types of nucleic acid sensors, play a vital role in the initial stage of innate immune response [1]. Substantial evidences have indicated that inflammation plays critical driving roles on tumor progress and metastasis, and several regulation mechanisms of PRR family genes in tumor proliferation and progression have been demonstrated in the past few years [3]. Several PRRs have been proved to inhibit tumor progression, such as deficiency of retinoic acid-inducible gene-I (RIG-I) can promote hepatocellular carcinoma (HCC) carcinogenesis [7]. Pattern recognition receptors (PRRs) family plays a vital role in the initial stage of innate immune response and the subsequent activation of adaptive immunity. Increasing evidences have indicated that several PRRs play critical roles in the progress of inflammation and tumorigenesis. The comprehensive significance of PRRs family in clinical prognosis of different cancers is still elusive
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