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Artigo Produção Nacional Revisado por pares
BIBTEX RIS

High infiltration of B cells in tertiary lymphoid structures, TCR oligoclonality, and neoantigens are part of esophageal squamous cell carcinoma microenvironment

2020; Oxford University Press; Volume: 108; Issue: 4 Linguagem: Inglês

10.1002/jlb.5ma0720-710rrr

ISSN

1938-3673

Autores

Luciana Rodrigues Carvalho Barros, Paulo Thiago de Souza-Santos, Marco Antônio M. Pretti, Gustavo Fioravanti Vieira, Marcelo Alves de Souza Bragatte, Marcus Fabiano de Almeida Mendes, Martiela Vaz de Freitas, Nicole de Miranda Scherer, Ivanir Martins de Oliveira, Davy Rapozo, Priscila Valverde Fernandes, Tatiana de Almeida Simão, Sheila Coelho Soares-Lima, Mariana Boroni, Luís Felipe Ribeiro Pinto, Martín Bonamino,

Tópico(s)

Monoclonal and Polyclonal Antibodies Research

Resumo

Abstract Esophageal squamous cell carcinoma (ESCA) exhibits high intratumoral molecular heterogeneity posing a challenge to cancer therapy. Immune checkpoint blockade therapy has been approved for this disease, but with modest results. RNA-Seq data from paired tumor and surrounding nonmalignant tissue from 14 patients diagnosed with ESCA without previous treatment and from The Cancer Genome Atlas-ESCA cohort were analyzed. Herein, we investigated ESCA immune landscape including mutation-derived neoantigens and immune cell subpopulations. Tumor-associated antigen expression was determined by in silico analyses and confirmed by immunohistochemistry showing that PRAME, CEACAM4, and MAGEA11 proteins are expressed on tumors. Immune checkpoint molecules gene expression was higher in the tumor compared with surrounding nonmalignant tissue, but its expression varies greatly among patients. TCR repertoire and BCR transcripts analysis evidenced low clonal diversity with one TCR clone predicted to be specific for a MAGEA11-derived peptide. A high number of B-cell clones infiltrating the tumors and the abundance of these cells in tertiary lymphoid structures observed in ESCA tumors support B cells as a potential immune modulator in this tumor.

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