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. 2026 Jul 1;17:1850228. doi: 10.3389/fimmu.2026.1850228

Figure 3.

Thyroid cancer immune context illustration distinguishing ATC-like and PDTC-like subtypes, with four tumor microenvironment categories: hot, altered immunosuppressed, cold, and altered excluded. Image shows varying combinations of cancer cells, CD8+ T cells, Tregs, dying cancer cells, and fibroblasts. Below, therapeutic algorithms are tailored by immune status, recommending options like immune checkpoint inhibitors, CSF-1R/TIGIT blockade, PD-1 blockade, Treg/M2 targeting, VEGFR-TKI, antigen vaccines, anti-angiogenic therapies, and oncolytic viruses. Legend explains cell types using colored shapes for clarity.

A novel classification method for thyroid cancer based on immunophenotypic characteristics and potential therapeutic strategies. This diagram stratifies thyroid tumors into four immunophenotypic categories, hot (ATC-like), altered immunosuppressed, cold, and altered excluded (PDTC-like), based on immune infiltration and functional status. For hot tumors, initial PD-1/CTLA-4 blockade may be effective, while progression warrants combinatorial strategies (e.g., CSF-1R or TIGIT inhibitors). In altered immunosuppressed tumors, therapies targeting Tregs or M2 macrophages are prioritized. Cold tumors require immune priming via radiation, viral therapies, or personalized neoantigen vaccines before PD-1 blockade. Altered excluded tumors benefit from stromal modulation (e.g., anti-angiogenics or focal radiotherapy) to enhance T-cell trafficking prior to ICI. This immunologic framework offers a rationale for precision immunotherapy in advanced thyroid cancer.