title: Differentiated thyroid carcinomas may elude the immune system by B7H1 upregulation.
abstract: B7H1 is consistently associated with inhibition of the immune system in many solid tumors. However, there is no report about its impact on differentiated thyroid carcinoma (DTC) presentation, aggressiveness, or evolution. Aiming to investigate the role of B7H1 in DTC and correlate this protein with other tumor-infiltrating immune cells, we studied 407 thyroid nodule tissue samples including 293 from DTC patients, all managed according to a same standard protocol. In addition, we obtained 5 normal and 114 benign thyroid lesions. Eighteen out of the 253 papillary thyroid carcinomas were paired with respective metastatic lymph node tissues. B7H1 (CD274) protein expression was assessed by immunohistochemistry and the gene expression was quantified by real-time PCR. Malignant tissues displayed a more intense B7H1 staining and higher mRNA levels than benign tissues (both P<0.0001). We observed a positive linear correlation between higher age at diagnosis and B7H1 mRNA levels (P=0.02896). Elevated levels of B7H1 protein were associated with the presence of CD4+, CD8+, CD20+, and FoxP3+ lymphocytes (all P<0.05); tumor-associated macrophages (P<0.0001); and the presence of myeloid-derived suppressor cells (P=0.03256). Stage II-IV patients presented higher B7H1 mRNA levels than stage I cases (P=0.03522). On the contrary, a decreased expression of B7H1 protein was observed in lymph node metastasis (P=0.0152). In conclusion, our data demonstrate that B7H1 expression is associated with features of aggressiveness, suggesting that this is an immune evasion mechanism of DTC cells.
authors.affiliation: Laboratory of Cancer Molecular Genetics, Faculty of Medical Sciences, University of Campinas, 126 Tessalia Vieira de Camargo Street, Campinas, São Paulo, Brazil.
authors.forename: Lucas Leite
authors.initials: LL
authors.lastname: Cunha
authors.forename: Marjory Alana
authors.initials: MA
authors.lastname: Marcello
authors.forename: Elaine Cristina
authors.initials: EC
authors.lastname: Morari
authors.forename: Suely
authors.initials: S
authors.lastname: Nonogaki
authors.forename: Fábio Frangiotti
authors.initials: FF
authors.lastname: Conte
authors.forename: René
authors.initials: R
authors.lastname: Gerhard
authors.forename: Fernando Augusto
authors.initials: FA
authors.lastname: Soares
authors.forename: José
authors.initials: J
authors.lastname: Vassallo
authors.forename: Laura Sterian
authors.initials: LS
authors.lastname: Ward
mesh_terms: D000328:Adult; D000368:Aged; D060890:B7-H1 Antigen / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D002291:Carcinoma, Papillary / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D002454:Cell Differentiation; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008207:Lymphatic Metastasis; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013961:Thyroid Gland / Q000276:immunology / Q000378:metabolism*; D013964:Thyroid Neoplasms / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D055815:Young Adult
chemical_list: D060890:B7-H1 Antigen; C423236:CD274 protein, human; D012333:RNA, Messenger