High infiltration of B cells in tertiary lymphoid structures, TCR oligoclonality, and neoantigens are part of esophageal squamous cell carcinoma microenvironment
| Autor: | Davy C M Rapozo, Martín Hernán Bonamino, Tatiana de Almeida Simão, Gustavo Fioravanti Vieira, Marco Antonio Pretti, Marcelo Alves de Souza Bragatte, Nicole de Miranda Scherer, Luis Felipe Ribeiro Pinto, Sheila Coelho Soares-Lima, Luciana Rodrigues Carvalho Barros, Marcus Fabiano de Almeida Mendes, Paulo Thiago de Souza-Santos, Priscila Valverde Fernandes, Mariana Boroni, Martiela Vaz de Freitas, Ivanir Martins de Oliveira |
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| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine Esophageal Neoplasms Immunology Receptors Antigen T-Cell Biology 03 medical and health sciences Lymphocytes Tumor-Infiltrating 0302 clinical medicine Immune system Antigen Antigens Neoplasm Tumor Microenvironment Humans Immunology and Allergy RNA-Seq B-Lymphocytes PRAME Tumor-infiltrating lymphocytes T-cell receptor breakpoint cluster region Cell Biology Immune checkpoint Tertiary Lymphoid Structures 030104 developmental biology 030220 oncology & carcinogenesis Cancer research Immunohistochemistry Female Esophageal Squamous Cell Carcinoma |
| Zdroj: | Journal of Leukocyte Biology. 108:1307-1318 |
| ISSN: | 1938-3673 0741-5400 |
| DOI: | 10.1002/jlb.5ma0720-710rrr |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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