Exploring markers of immunoresponsiveness in papillary thyroid carcinoma and future treatment strategies

Abstract

BackgroundThe study summarizes the potential use of immunotherapy forBRAF-mutated papillary thyroid cancer (PTC) by analyzing the immune profile of City of Hope PTC patient samples and comparing them to the thyroid dataset available in the TCGA database.Materials and methodsPTC cases with available formalin-fixed paraffin-embedded archived tumor tissue were identified. RNA was extracted from the tumor tissue and analyzed by NanoString to evaluate their immune gene expression profile. Immunohistochemistry was used to determine the expression of immune suppressive genes and lymphocytic infiltration into the tumor tissue. Thyroid cancer cell lines (MDA-T32, MDA-T68, MDA-T85, and MDA-T120) were used to determine the correlation between the BRAF inhibition and CD274 expression.ResultsThe study found that PTC cases withBRAFmutations had higher expression of immune checkpoint markers CD274 and CTLA4, as well as higher tumor-infiltrating lymphocytes, particularly CD4+T cells. Additionally, the study identified immunosuppressive markers expressed by tumor cells like CD73, CD276, and CD200 that could be targeted for immunotherapy. Further experiments using PTC cell lines lead to the conclusion that CD274 expression correlates withBRAFactivity and that inhibitors ofBRAFcould potentially be used in combination with immunotherapy to treat PTC.ConclusionsThese findings suggest that PTC cases withBRAFmutations or high expression may be correlated with an immune hot signature and could benefit from immunotherapeutic strategies.