Immunohistochemical characterization of immune cell infiltration in paediatric and adult Langerhans cell histiocytosis

Autor(es)

Yacarini Paredes, Silvia Elena ^[1] ; Almeida, Luciana Yamamoto ^[2] ; Trevisan, Glauce Lunardelli ^[3] ; Jimenez Polanco, Xiomara Beatriz ^[1] ; Silveira, Heitor Albergoni ^[4] ; Silva, Evanio Vilela ^[4] ; Bezerra Segato, Raquel Assed ^[1] ; Bezerra da Silva, Lea Assed ^[1] ; Chahud, Fernando ^[3] ; Leon, Jorge Esquiche ^[4]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo FORP USP, Sch Dent Ribeirao Preto, Dept Pediat Dent, Ribeirao Preto - Brazil

^[2] Univ Sao Paulo, Ribeirao Preto Med Sch FMRP USP, Dept Clin Med, Hematol Div, Ribeirao Preto - Brazil

^[3] Univ Sao Paulo, Ribeirao Preto Med Sch FMRP USP, Dept Pathol & Forens Med, BR-14049900 Ribeirao Preto, SP - Brazil

^[4] Univ Sao Paulo FORP USP, Sch Dent Ribeirao Preto, Dept Stomatol, Oral Pathol, Publ Oral Hlth & Forens Dent, BR-14040904 Ribeirao Preto, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Scandinavian Journal of Immunology; v. 92, n. 6 AUG 2020.
• Citações Web of Science: 0

Resumo

Langerhans cell histiocytosis (LCH) is an inflammatory myeloid neoplasia commonly affecting children with frequent somatic mutations in MAPK pathway genes including BRAF(V600E)and MAP2K1. Some studies suggest that LCH cells can recruit and modulate inflammatory cells, which could provide reciprocal survival signals. To characterize the immune profile of infiltrating inflammatory cells, and to clarify their participation in LCH pathogenesis, a detailed immunohistochemical analysis was performed. Fifteen (10 children, 5 adults) LCH cases were assessed through macrophage (CD68 and CD163), mature dendritic cell (mDC; CD83 and CD208), regulatory T cell (Treg; CD4, CD25 and FOXP3) and cytotoxic lymphocyte (CL; CD56, CD57, perforin and granzyme B) immunomarkers. Moreover, lymphocytic and LCH markers were also analysed. All cases were S100, CD1a, CD207 and CD4-positive. Bcl-2 and cyclin D1 expression was observed in 13 of 15 cases. In the immune microenvironment, M2-polarized macrophages and Tregs were the predominant cell populations, followed by significantly (P < .005) smaller levels of mDCs and CLs. Additionally, the number of CD3 + cells was significantly higher than that of CD20 + cells. In the CD3 + cell population, there were a significantly higher number of CD4 + cells than CD8 + cells. While there were no differences when comparing the paediatric and adult populations, FOXP3 + cells were significantly higher in patients with multisystem involvement and treated with chemotherapy, than single-site cases and those without chemotherapy. Our results suggest that M2-polarized macrophages and Treg infiltration can promote LCH development and survival, probably through pro-tumoral, immunosuppressive and/or cytokine-mediated mechanisms. This work highlights the need for further exploration of immune-targeted therapy for LCH. (AU)

• Processo FAPESP: 16/11419-0 - Correlação clinicopatológica do grau de diferenciação, expressão de tetraspaninas, agentes virais e proliferação celular em uma ampla série de carcinomas espinocelulares da região de cabeça e pescoço.
• Beneficiário: Jorge Esquiche León
• Modalidade de apoio: Auxílio à Pesquisa - Regular