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

• Published in: Journal of leukocyte biology Vol. 108; no. 4; pp. 1307 - 1318
• Main Authors: Barros, Luciana Rodrigues Carvalho, Souza‐Santos, Paulo Thiago De, Pretti, Marco Antonio Marques, Vieira, Gustavo Fioravanti, Bragatte, Marcelo Alves De Souza, Mendes, Marcus Fabiano De Almeida, De Freitas, Martiela Vaz, Scherer, Nicole De Miranda, De Oliveira, Ivanir Martins, Rapozo, Davy Carlos Mendes, Fernandes, Priscila Valverde, Simão, Tatiana De Almeida, Soares‐Lima, Sheila Coelho, Boroni, Mariana, Ribeiro Pinto, Luis Felipe, Bonamino, Martin Hernan
• Format: Journal Article
• Language: English
• Published: United States 01-10-2020
• Subjects: Antigens, Neoplasm - immunology; B-Lymphocytes - immunology; B-Lymphocytes - pathology; esophageal cancer; Esophageal Neoplasms - immunology; Esophageal Neoplasms - pathology; Esophageal Squamous Cell Carcinoma - immunology; Esophageal Squamous Cell Carcinoma - pathology; Female; Humans; Lymphocytes, Tumor-Infiltrating - immunology; Lymphocytes, Tumor-Infiltrating - pathology; Male; neoantigens; oncoimmunology; Receptors, Antigen, T-Cell - immunology; RNA-Seq; Tertiary Lymphoid Structures - immunology; Tertiary Lymphoid Structures - pathology; Tumor Microenvironment - immunology; tumor‐infiltrating lymphocytes; neoantigens; tumor-infiltrating lymphocytes; esophageal cancer; oncoimmunology
• ISSN: 0741-5400; 1938-3673
• DOI: 10.1002/JLB.5MA0720-710RRR

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.
Graphical
B lymphocytes are an important component of tumor‐associated tertiary lymphoid organ structures and may be a potential immune modulator in ESCA.