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Gatenbee, C.

Publications and source records attributed to Gatenbee, C..

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NeoPredPipe: High-Throughput Neoantigen Prediction and Recognition Potential Pipeline

Next generation sequencing has yielded an unparalleled means of quickly determining the molecular make-up of patient tumors. In conjunction with emerging, effective immunotherapeutics for a number of cancers, this rapid data generation necessitates a paired high-throughput means of predicting and assessing neoantigens from tumor variants that may stimulate immune response. Here we offer NeoPredPipe (Neoantigen Prediction Pipeline) as a contiguous means of predicting putative neoantigens and their corresponding recognition potentials for both single and multi-region tumor samples. NeoPredPipe is able to quickly provide summary information for researchers, and clinicians alike, on neoantigen burdens while providing high-level insights into tumor heterogeneity given somatic mutation calls and, optionally, patient HLA haplotypes. Given an example dataset we show how NeoPredPipe is able to rapidly provide insights into neoantigen heterogeneity, burden, and immune stimulation potential. Through the integration of widely adopted tools for neoantigen discovery NeoPredPipe offers a contiguous means of processing single and multi-region sequence data. NeoPredPipe is user-friendly and adaptable for high-throughput performance. NeoPredPipe is freely available at https://github.com/MathOnco/NeoPredPipe.

bioinformatics

Acidity promotes tumor progression by altering macrophage phenotype in prostate cancer

Tumors rapidly ferment glucose to lactic acid even in the presence of oxygen, and coupling high glycolysis with poor perfusion leads to extracellular acidification. Here we demonstrate that acidity, independent from lactate, augments the pro-tumor phenotype of macrophages. We used zwitterionic buffers to show that activating macrophages at pH 6.8 in vitro enhanced an IL-4-driven phenotype as measured by gene expression, cytokine profiling, and functional assays. These results were recapitulated in vivo wherein neutralizing intratumoral acidity reduced the pro-tumor phenotype of macrophages, while also decreasing tumor incidence and invasion in the TRAMP model of prostate cancer. These results were recapitulated using an in silico mathematical model that simulate macrophage responses to environmental signals. By turning off acid-induced cellular responses, our in silico mathematical modeling shows that acid-resistant macrophages can limit tumor progression. In summary, this study suggests that tumor acidity contributes to prostate carcinogenesis by altering the state of macrophage activation.

immunology