Tumor-Infiltrating B- and T-Cell Repertoire in Pancreatic Cancer Associated With Host and Tumor Features

• DOI: 10.3389/fimmu.2021.730746
• Publication Date: 2021-09-23T07:25:56Z
• Authors: Silvia Pineda; Evangelina López ...; Katharine Yu; Akshay Ravoor; Inés Wood; Núria Malats; Marina Sirota
• Keywords: Male; 0301 basic medicine; T-Lymphocytes; pancreatic cancer; immunoglobulins; 2404.01 Bioestadística; Risk Factors; Receptors; Databases, Genetic; Tumor Microenvironment; 2.1 Biological and endogenous factors; Compositional analysis; Lymphocytes; RNA-Seq; Aetiology; Cancer; B-Lymphocytes; Smoking; Bioinformática; Middle Aged; Prognosis; 3. Good health; compositional analysis; Phenotype; Tumor microenvironment; Pancreatic Ductal; Medical Microbiology; Antigen; B-cell repertoire; T-cell repertoire; Female; Carcinoma, Pancreatic Ductal; 612.017; Adult; 2412 Inmunología; Oncology and Carcinogenesis; Immunology; Inmunología; Receptors, Antigen, T-Cell; 610; Immunoglobulins; Pancreatic Cancer; Databases; Tumor infiltration; 03 medical and health sciences; Rare Diseases; Lymphocytes, Tumor-Infiltrating; Sex Factors; Genetic; Genetics; tumor microenvironment; Humans; Tumor-Infiltrating; Aged; 519.2:57; Biomedical and Clinical Sciences; Gene Expression Profiling; Carcinoma; Pancreatic cancer; RC581-607; T-Cell; Pancreatic Neoplasms; Good Health and Well Being; Biochemistry and cell biology; tumor infiltration; Immunologic diseases. Allergy; Digestive Diseases; Transcriptome

BackgroundInfiltrating B and T cells have been observed in several tumor tissues, including pancreatic ductal adenocarcinoma (PDAC). The majority known PDAC risk factors point to a chronic inflammatory process leading to different forms of immunological infiltration. Understanding pancreatic tumor infiltration may lead to improved knowledge of this devastating disease.MethodsWe extracted the immunoglobulins (IGs) and T cell receptors (TCRs) from RNA-sequencing of 144 PDAC from TCGA and 180 pancreatic normal tissue from GTEx. We used Shannon entropy to find differences in IG/TCR diversity. We performed a clonotype analysis considering the IG clone definition (same V and J segments, same CDR3 length, and 90% nucleotide identity between CDR3s) to study differences among the tumor samples. Finally, we performed an association analysis to find host and tumor factors associated with the IG/TCR.ResultsPDAC presented a richer and more diverse IG and TCR infiltration than normal pancreatic tissue. A higher IG infiltration was present in heavy smokers and females and it was associated with better overall survival. In addition, specific IG clonotypes classified samples with better prognosis explaining 24% of the prognosis phenotypic variance. On the other hand, a larger TCR infiltration was present in patients with previous history of diabetes and was associated with lower nonantigen load.ConclusionsOur findings support PDAC subtyping according to its immune repertoire landscape with a potential impact on the understanding of the inflammatory basis of PDAC risk factors as well as the design of treatment options and prognosis monitoring.