RT Journal Article
SR Electronic
T1 Exploring markers of immunoresponsiveness in papillary thyroid carcinoma and future treatment strategies
JF Journal for ImmunoTherapy of Cancer
JO J Immunother Cancer
FD BMJ Publishing Group Ltd
SP e008505
DO 10.1136/jitc-2023-008505
VO 12
IS 7
A1 Mohanty, Atish
A1 Afkhami, Michelle
A1 Reyes, Amanda
A1 Pharaon, Rebecca
A1 Yin, Holly
A1 Li, Haiqing
A1 Do, Dana
A1 Bell, Diana
A1 Nam, Arin
A1 Chang, Sue
A1 Gernon, Thomas
A1 Kang, Robert
A1 Amini, Arya
A1 Sampath, Sagus
A1 Kulkarni, Prakash
A1 Pillai, Raju
A1 Villaflor, Vicky
A1 Salgia, Ravi
A1 Maghami, Ellie
A1 Massarelli, Erminia
YR 2024
UL http://jitc.bmj.com/content/12/7/e008505.abstract
AB Background The study summarizes the potential use of immunotherapy for BRAF-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 methods PTC 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.Results The study found that PTC cases with BRAF mutations 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 with BRAF activity and that inhibitors of BRAF could potentially be used in combination with immunotherapy to treat PTC.Conclusions These findings suggest that PTC cases with BRAF mutations or high expression may be correlated with an immune hot signature and could benefit from immunotherapeutic strategies.All data relevant to the study are included in the article or uploaded as online supplemental information. Not Aapplicable.