RESUMEN

Esophageal adenocarcinoma (EAC) develops from Barrett's esophagus (BE), a chronic inflammatory state that can progress through a series of transformative dysplastic states before tumor development. While molecular and genetic changes of EAC tumors have been studied, immune microenvironment changes during Barrett's progression to EAC remain poorly understood. In this study, we identify potential immunologic changes that can occur during BE-to-EAC progression. RNA sequencing (RNA-Seq) analysis on tissue samples from EAC patients undergoing surgical resection demonstrated that a subset of chemokines and cytokines, most notably IL6 and CXCL8, increased during BE progression to EAC. xCell deconvolution analysis investigating immune cell population changes demonstrated that the largest changes in expression during BE progression occurred in M2 macrophages, pro-B cells, and eosinophils. Multiplex immunohistochemical staining of tissue microarrays showed increased immune cell populations during Barrett's progression to high-grade dysplasia. In contrast, EAC tumor sections were relatively immune poor, with a rise in PD-L1 expression and loss of CD8+ T cells. These data demonstrate that the EAC microenvironment is characterized by poor cytotoxic effector cell infiltration and increased immune inhibitory signaling. These findings suggest an immunosuppressive microenvironment, highlighting the need for further studies to explore immune modulatory therapy in EAC.

Asunto(s)

Adenocarcinoma/inmunología , Esófago de Barrett/inmunología , Neoplasias Esofágicas/inmunología , Adenocarcinoma/genética , Adenocarcinoma/patología , Esófago de Barrett/genética , Esófago de Barrett/patología , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/inmunología , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/patología , Quimiocinas/genética , Quimiocinas/metabolismo , Citocinas/genética , Citocinas/metabolismo , Progresión de la Enfermedad , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patología , Humanos , Tolerancia Inmunológica , Inmunohistoquímica , Interleucina-6/genética , Interleucina-6/metabolismo , Interleucina-8/genética , Interleucina-8/metabolismo , Macrófagos/inmunología , Macrófagos/patología , RNA-Seq , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/patología , Microambiente Tumoral/genética , Microambiente Tumoral/inmunología

RESUMEN

BetterKatz is a bacteriophage isolated from a soil sample collected in Pittsburgh, Pennsylvania using the host Gordonia terrae 3612. BetterKatz's genome is 50,636 bp long and contains 75 predicted protein-coding genes, 35 of which have been assigned putative functions. BetterKatz is not closely related to other sequenced Gordonia phages.

RESUMEN

Gordonia phages Bowser and Schwabeltier are newly isolated phages infecting Gordonia terrae 3612. Bowser and Schwabeltier have similar siphoviral morphologies and their genomes are related to each other, but not to other phages. Their lysis cassettes are atypically situated among virion tail genes, and Bowser encodes two tyrosine integrases.

RESUMEN

Emalyn is a newly isolated bacteriophage of Gordonia terrae 3612 and has a double-stranded DNA genome 43,982 bp long with 67 predicted protein-encoding genes, 32 of which we can assign putative functions. Emalyn has a prolate capsid and has extensive nucleotide similarity with several previously sequenced phages.

RESUMEN

Mycobacteriophages Cambiare, FlagStaff, and MOOREtheMARYer are newly isolated phages of Mycobacterium smegmatis mc(2) 155 recovered from soil samples in Pittsburgh, PA. All three genomes are closely related to cluster G mycobacteriophages but differ sufficiently in nucleotide sequence and gene content to warrant division of cluster G into several subclusters.