Research Paper Volume 13, Issue 5 pp 6740—6751
Interleukin-33 modulates immune responses in cutaneous melanoma in a context-specific way
- 1 Department of Otorhinolaryngology Head and Neck Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, Guangdong, China
- 2 Institute of Otorhinolaryngology Head and Neck Surgery, Sun Yat-sen University, Guangzhou 510080, Guangdong, China
- 3 Department of Otorhinolaryngology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, Guangdong, China
Received: September 14, 2020 Accepted: December 29, 2020 Published: February 17, 2021
https://doi.org/10.18632/aging.202531How to Cite
Copyright: © 2021 Peng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Controversial roles of interleukin-33 (IL-33) have been reported in melanoma from animal studies. We aimed to investigate the role of IL-33 in human cutaneous melanoma. RNA-seq data of 471 cases of cutaneous melanoma were retrieved from The Cancer Genome Atlas. The tumor microenvironment (TME) was deconstructed by the xCell algorithm using RNA-seq data. We evaluated the prognostic value of IL-33 and the relationship between IL-33 and immune components in TME. We also inferred the potential cellular sources of IL-33. All the analyses were conducted separately in three sub-cohorts, which are based on the biopsy sites of samples: primary melanoma; lymph node (LN) metastases; other metastases, including metastases to skin/soft tissue, or visceral sites. In the two metastasis sub-cohorts, IL-33 is associated with better prognosis and more active immune responses in the tumor. However, IL-33 is not a prognostic factor in the primary melanoma sub-cohort. Furthermore, we found that IL-33 is mainly derived from stromal cells in the metastasis sub-cohorts, and from epithelial cells/keratinocytes in the primary melanoma sub-cohort. These findings provide evidence for the context-specific anti-tumor effects of IL-33 in melanoma. And the distinct effects of IL-33 may be determined by the cellular sources of IL-33.
Abbreviations
IL-33: interleikin-33; NK cell: natural killer cell; IFN-γ: interferon-γ; DC: dendritic cell; Treg cell: regulatory T cell; ILC2: group 2 innate lymphoid cell; TCGA: The Cancer Genome Atlas; RNA-seq: RNA-sequencing; TME: tumor microenvironment; LN: lymph node; OS: overall survival; PFS: progression-free survival; Th1 cell: type 1 T helper cell; NKT cell: natural killer T cell; KEGG: Kyoto Encyclopedia of Genes and Genomes; RSEM: RNA-Seq by Expectation Maximization.