Immune Profiling of Advanced Thyroid Cancers Using Fluorescent Multiplex Immunohistochemistry

Area of Science:

• Oncology
• Immunology
• Pathology

Background:

• Advanced thyroid cancers, including differentiated thyroid carcinoma (DTC) with distant metastasis and anaplastic thyroid carcinoma (ATC), present poor prognoses and limited therapeutic strategies.
• Understanding the tumor immune microenvironment is crucial for developing effective treatments for these aggressive cancers.

Purpose of the Study:

• To investigate and compare the immune profiles of advanced DTC and ATC.
• To assess the expression of programmed cell death-ligand 1 (PD-L1) and immune cell infiltration in these tumor types.

Main Methods:

• Utilized fluorescent multiplex immunohistochemistry (F-MIHC) and multispectral imaging (MSI) on 28 tissue samples from 12 DTC and 16 ATC patients.
• Analyzed expression of CD4, CD8, PD-1, PD-L1, forkhead box protein 3, and cytokeratin (CK).
• Evaluated PD-L1 expression using tumor proportion score (TPS) and combined positive score (CPS).

Main Results:

• Anaplastic thyroid carcinoma (ATC) samples exhibited significantly higher PD-L1-positive tumor cells (CK+PD-L1+) per mm² compared to DTC samples (183.5 vs. 0.03, p < 0.001).
• ATC showed increased lymphocyte infiltration, including significantly more PD-L1- or PD-1-positive lymphocytes than DTC.
• PD-L1 expression (TPS and CPS) was negative in all DTC samples but positive in 81% and 94% of ATC samples, respectively.

Conclusions:

• Significant differences in immune profiles, particularly PD-L1 expression and lymphocyte infiltration, exist between advanced DTC and ATC.
• Immune profiling via F-MIHC and MSI provides valuable insights into tumor microenvironments.
• This approach can aid in identifying suitable candidates for immunotherapy in advanced thyroid cancers.