Abstract
Within the endocrine system, thyroid cancer (THCA) is the most typical malignant tumor. Tumor-infiltrating immune cells play vital roles in tumor progression, recurrence, metastasis as well as response to immunotherapy. However, THCA’s immune infiltrative landscape is still not clarified. Therefore, we utilized two statistical algorithms to investigate the immune cell infiltration (ICI) landscape of 505 THCA samples and defined three ICI immune subtypes. The ICI scores were calculated using principal-component analysis. Increased tumor mutation burden (TMB) and immune-related signaling pathways were associated to a high ICI score. The high ICI score group indicated a relatively longer overall survival (OS) than the low ICI score group. Most immune checkpoint-related and immune activation-related genes were considerably upregulated in the ICI high group, which indicates stronger immunogenicity and a greater likelihood of benefiting from immunotherapy. In two cohort studies of patients receiving immunotherapy, high-ICI-score group showed notable therapeutic effects and clinical advantages compared to those with lower ICI scores. These results demonstrate that ICI score acts as an effective prognostic indicator and predictor of response to immunotherapy.
Highlights
The most common malignant tumor of the endocrine system is thyroid cancer (THCA)
An early clinical trial showed that the PD-1 inhibitor pembrolizumab may be safe and effective in treating PD-L1positive thyroid cancer
The ICI3 subtype with poor prognosis was characterized by low CD8+ T cell infiltration, high infiltration of static memory CD4+ T cells and active dendritic cells (DCs), and a high stromal score
Summary
The most common malignant tumor of the endocrine system is thyroid cancer (THCA). As tumor detection has advanced, the global incidence of THCA has risen rapidly. Younger people and women are more likely to suffer from it (La Vecchia et al, 2015; Du et al, 2018; Siegel et al, 2020). There are four major pathological subtypes of thyroid cancer: papillary thyroid carcinoma, follicular thyroid carcinoma, medullary thyroid carcinoma, and undifferentiated carcinoma. The prognoses vary greatly (Cabanillas et al, 2016). Traditional treatments including chemotherapy and radiotherapy cannot improve the therapeutic effect of locally advanced or metastatic thyroid cancer, which makes the development of effective treatments crucial
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