Department of Otorhinolaryngology Head and Neck Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, Guangdong, China.
Institute of Otorhinolaryngology Head and Neck Surgery, Sun Yat-sen University, Guangzhou 510080, Guangdong, China.
Aging (Albany NY). 2021 Feb 17;13(5):6740-6751. doi: 10.18632/aging.202531.
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.
IL-33 在黑色素瘤中的作用存在争议，已有动物研究报道。我们旨在研究 IL-33 在人类皮肤黑色素瘤中的作用。从癌症基因组图谱中检索了 471 例皮肤黑色素瘤的 RNA-seq 数据。使用 RNA-seq 数据，通过 xCell 算法对肿瘤微环境（TME）进行了重构。我们评估了 IL-33 的预后价值以及其与 TME 中免疫成分之间的关系。我们还推断了 IL-33 的潜在细胞来源。所有分析均分别在三个亚队列中进行，这三个亚队列基于样本的活检部位：原发性黑色素瘤；淋巴结（LN）转移；其他转移，包括皮肤/软组织或内脏部位的转移。在两个转移亚队列中，IL-33 与肿瘤中更好的预后和更活跃的免疫反应相关。然而，在原发性黑色素瘤亚队列中，IL-33 不是预后因素。此外，我们发现 IL-33 主要来源于转移亚队列中的基质细胞，而来源于原发性黑色素瘤亚队列中的上皮细胞/角质形成细胞。这些发现为 IL-33 在黑色素瘤中的抗肿瘤作用提供了证据，且 IL-33 的不同作用可能取决于 IL-33 的细胞来源。
