Browsing by Author "Phillips, William"

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    In vivo optical imaging-guided targeted sampling for precise diagnosis and molecular pathology
    (2021) Sahu, Aditi; Oh, Yuna; Peterson, Gary; Cordova, Miguel; Navarrete-Dechent, Cristian; Gill, Melissa; Alessi-Fox, Christi; Gonzalez, Salvador; Phillips, William; Wilson, Steven; Afzalneia, Reza; Rose, Raven; Mohsere, Abu-Akeel; Bello, Danielle; Marghoob, Ashfaq; Rossi, Anthony; Wolchok, Jedd D.; Merghoub, Taha; Rotemberg, Veronica; Chen, Chih-Shan Jason; Rajadhyaksha, Milind
    Conventional tissue sampling can lead to misdiagnoses and repeated biopsies. Additionally, tissue processed for histopathology suffers from poor nucleic acid quality and/or quantity for downstream molecular profiling. Targeted micro-sampling of tissue can ensure accurate diagnosis and molecular profiling in the presence of spatial heterogeneity, especially in tumors, and facilitate acquisition of fresh tissue for molecular analysis. In this study, we explored the feasibility of performing 1-2 mm precision biopsies guided by high-resolution reflectance confocal microscopy (RCM) and optical coherence tomography (OCT), and reflective metallic grids for accurate spatial targeting. Accurate sampling was confirmed with either histopathology or molecular profiling through next generation sequencing (NGS) in 9 skin cancers in 7 patients. Imaging-guided 1-2 mm biopsies enabled spatial targeting for in vivo diagnosis, feature correlation and depth assessment, which were confirmed with histopathology. In vivo 1-mm targeted biopsies achieved adequate quantity and high quality of DNA for next-generation sequencing. Subsequent mutational profiling was confirmed on 1 melanoma in situ and 2 invasive melanomas, using a 505-gene mutational panel called Memorial Sloan Kettering-Integrated mutational profiling of actionable cancer targets (MSK-IMPACT). Differential mutational landscapes, in terms of number and types of mutations, were found between invasive and in situ melanomas in a single patient. Our findings demonstrate feasibility of accurate sampling of regions of interest for downstream histopathological diagnoses and molecular pathology in both in vivo and ex vivo settings with broad diagnostic, therapeutic and research potential in cutaneous diseases accessible by RCM-OCT imaging.
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    In vivo tumor immune microenvironment phenotypes correlate with inflammation and vasculature to predict immunotherapy response
    (2022) Sahu, Aditi; Kose, Kivanc; Kraehenbuehl, Lukas; Byers, Candice; Holland, Aliya; Tembo, Teguru; Santella, Anthony; Alfonso, Anabel; Li, Madison; Cordova, Miguel; Gill, Melissa; Fox, Christi; Gonzalez, Salvador; Kumar, Piyush; Wang, Amber Weiching; Kurtansky, Nicholas; Chandrani, Pratik; Yin, Shen; Mehta, Paras; Navarrete-Dechent, Cristian; Peterson, Gary; King, Kimeil; Dusza, Stephen; Yang, Ning; Liu, Shuaitong; Phillips, William; Guitera, Pascale; Rossi, Anthony; Halpern, Allan; Deng, Liang; Pulitzer, Melissa; Marghoob, Ashfaq; Chen, Chih-Shan Jason; Merghoub, Taha; Rajadhyaksha, Milind
    Response to immunotherapies can be variable and unpredictable. Pathology-based phenotyping of tumors into 'hot' and 'cold' is static, relying solely on T-cell infiltration in single-time single-site biopsies, resulting in suboptimal treatment response prediction. Dynamic vascular events (tumor angiogenesis, leukocyte trafficking) within tumor immune microenvironment (TiME) also influence anti-tumor immunity and treatment response. Here, we report dynamic cellular-level TiME phenotyping in vivo that combines inflammation profiles with vascular features through non-invasive reflectance confocal microscopic imaging. In skin cancer patients, we demonstrate three main TiME phenotypes that correlate with gene and protein expression, and response to toll-like receptor agonist immune-therapy. Notably, phenotypes with high inflammation associate with immunostimulatory signatures and those with high vasculature with angiogenic and endothelial anergy signatures. Moreover, phenotypes with high inflammation and low vasculature demonstrate the best treatment response. This non-invasive in vivo phenotyping approach integrating dynamic vasculature with inflammation serves as a reliable predictor of response to topical immune-therapy in patients.
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    Quantifying the effects of driver non-compliance and communication system failure in the performance of real-time bus control strategies
    (2015) Phillips, William; Del Rio, Andrés; Muñoz Abogabir, Juan Carlos; Delgado Breinbauer, Felipe Alberto; Giesen Encina, Ricardo; CEDEUS (Chile)