Immune Cell Confrontation in the Papillary Thyroid Carcinoma Microenvironment

Area of Science:

• Oncology
• Immunology
• Genomics

Background:

• Papillary thyroid cancer (PTC) is linked to chronic inflammation.
• Understanding immune cell infiltration in PTC is crucial for developing new diagnostic and therapeutic strategies.

Purpose of the Study:

• To systematically analyze immune cell infiltration in PTC.
• To identify differences in immune cell profiles between normal and cancerous thyroid tissues, and between early and advanced PTC.
• To explore the mechanisms underlying immune response variations in PTC.

Main Methods:

• Utilized ssGSEA, immune cell marker analysis, and CIBERSORT across 10 datasets (TCGA and others) comprising 799 PTC and 194 normal samples.
• Employed consensus unsupervised clustering to categorize PTC patients into low-immunity and high-immunity groups.
• Applied WGCNA and GSEA to investigate mechanisms driving immune response differences.

Main Results:

• PTC tissues exhibited higher overall immune levels and increased abundance of M2 macrophages, Tregs, monocytes, neutrophils, dendritic cells (DCs), mast cells (MCs), and M0 macrophages compared to normal tissues.
• Advanced PTC showed greater immune infiltration and higher levels of these tumor-promoting immune cells compared to early-stage PTC.
• The high-immunity group was associated with more advanced stages, larger tumors, lymph node metastasis, specific PTC subtypes (tall-cell), BRAF mutations, and Epstein-Barr virus (EBV) infection.

Conclusions:

• M2 macrophages, Tregs, monocytes, neutrophils, DCs, MCs, and M0 macrophages likely promote tumor growth in PTC, while M1 macrophages, CD8+ T cells, B cells, NK cells, and T follicular helper cells may have antitumor roles.
• Increased immune infiltration and abundance of tumor-promoting cells during PTC development suggest aggravated immune escape.
• Epstein-Barr virus (EBV) may significantly influence the immune microenvironment in PTC.