Browsing by Author "Sahu, Aditi"

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    Differential expression of programmed cell death ligand 1 (PD-L1) and inflammatory cells in basal cell carcinoma subtypes
    (2022) Gompertz-Mattar, Matias; Perales, Juan; Sahu, Aditi; Mondaca, Sebastian; Gonzalez, Sergio; Uribe, Pablo; Navarrete-Dechent, Cristian
    Few studies have evaluated programmed cell death ligand (PD-L1) expression and lymphocytic infiltrates in Basal Cell Carcinoma (BCC). The objectives of this study are to assess PD-L1 expression and markers of local immune response in nodular, superficial, and morpheaform BCC, and compare it to normal, sun-exposed skin from the periphery of intradermal nevi. This was a retrospective study that included three histological subtypes of BCCs, and sun-exposed skin from the periphery of dermal nevi as quality controls. Tissue microarrays (TMA) were constructed with subsequent staining of H&E and immunohistochemistry (IHC) for CD4, CD8, FOXP3 and PD-L1. Non-automated quantification of the infiltrate in the intratumoral and stromal compartments on TMAs was performed. A total of 115 BCC (39 nodular, 39 morpheaform, and 37 superficial) and 41 sun-exposed skin samples were included (mean age 65.4 years; 52.6% females). BCC showed higher expression of PD-L1 (5.4 vs 0.7%, p < 0.001), CD8 (29.8 vs 19.7%, p = 0.002), and FOXP3 (0.3 vs 0.06%, p = 0.022) compared to sun-exposed skin. There was a higher PD-L1 expression in nodular BCC compared with other subtypes. Low-risk BCC subtypes (superficial and nodular) exhibited more PD-L1 expression in intratumoral and stromal immune infiltrates as compared to high-risk BCC subtypes. As a limitation, no immune cells function was evaluated in this study, only the presence/absence of T-lymphocyte sub-populations was recorded. Substantial differences in both PD-L1 expression and lymphocytic infiltrates were found amongst the histological subtypes of BCC and sun-exposed skin. Highest PD-L1 expression was found in nodular BCCs which suggests a potentially targetable strategy in the treatment of this most common BCC subtype.
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    Evaluation of a Combined Reflectance Confocal Microscopy-Optical Coherence Tomography Device for Detection and Depth Assessment of Basal Cell Carcinoma
    (2018) Sahu, Aditi; Yélamos, Oriol; Iftimia, Nicusor; Córdova, Miguel; Alessi Fox, Christi; Gill, Melissa; Maguluri, Gopi; Dusza, Stephen; Navarrete Dechent, Cristián Patricio; González, Salvador; Rossi, Anthony M.; Marghoob, Ashfaq A.; Rajadhyaksha, Milind; Chen, C-S J.
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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.