High infiltration of B cells in tertiary lymphoid structures, TCR oligoclonality, and neoantigens are part of esophageal squamous cell carcinoma microenvironment.
Luciana Rodrigues Carvalho BarrosPaulo Thiago De Souza-SantosMarco Antonio Marques PrettiGustavo Fioravanti VieiraMarcelo Alves De Souza BragatteMarcus Fabiano De Almeida MendesMartiela Vaz De FreitasNicole De Miranda SchererIvanir Martins De OliveiraDavy Carlos Mendes RapozoPriscila Valverde FernandesTatiana De Almeida SimãoSheila Coelho Soares-LimaMariana BoroniLuis Felipe Ribeiro PintoLuciana Rodrigues Carvalho BarrosPublished in: Journal of leukocyte biology (2020)
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.
Keyphrases
- single cell
- rna seq
- gene expression
- regulatory t cells
- cancer therapy
- poor prognosis
- ejection fraction
- induced apoptosis
- high resolution
- dna methylation
- stem cells
- newly diagnosed
- drug delivery
- papillary thyroid
- machine learning
- young adults
- squamous cell carcinoma
- signaling pathway
- atomic force microscopy
- mass spectrometry
- genome wide
- tyrosine kinase
- risk assessment
- climate change
- patient reported outcomes
- combination therapy
- human health