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115 results on '"Hoyt, Clifford"'

1. Multi-platform biomarkers of response to an immune checkpoint inhibitor in the neoadjuvant I-SPY 2 trial for early-stage breast cancer.

Author

Campbell, Michael, Wolf, Denise, Yau, Christina, Brown-Swigart, Lamorna, Wulfkuhle, Julie, Gallagher, Isela, Zhu, Zelos, Bolen, Jennifer, Vandenberg, Scott, Hoyt, Clifford, Mori, Hidetoshi, Borowsky, Alexander, Sit, Laura, Perlmutter, Jane, Asare, Smita, Nanda, Rita, Liu, Minetta, Yee, Douglas, DeMichele, Angela, Hylton, Nola, Pusztai, Lajos, Berry, Donald, Hirst, Gillian, Petricoin, Emanuel, Veer, Laura, and Esserman, Laura

Subjects
breast cancer, immune checkpoint blockade, multiplex immunofluorescence, predictive markers, spatial metrics, Humans, Female, Neoadjuvant Therapy, Breast Neoplasms, Immune Checkpoint Inhibitors, Biomarkers, Tumor, Tumor Microenvironment, B7-H1 Antigen, Neoplasm Staging, Middle Aged, Programmed Cell Death 1 Receptor, Treatment Outcome
Abstract

Only a subset of patients with breast cancer responds to immune checkpoint blockade (ICB). To better understand the underlying mechanisms, we analyze pretreatment biopsies from patients in the I-SPY 2 trial who receive neoadjuvant ICB using multiple platforms to profile the tumor microenvironment. A variety of immune cell populations and markers of immune/cytokine signaling associate with pathologic complete response (pCR). Interestingly, these differ by breast cancer receptor subtype. Measures of the spatial distributions of immune cells within the tumor microenvironment, in particular colocalization or close spatial proximity of PD-1+ T cells with PD-L1+ cells (immune and tumor cells), are significantly associated with response in the overall cohort as well as the in the triple negative (TN) and HR+HER2- subtypes. Our findings indicate that biomarkers associated with immune cell signaling, immune cell densities, and spatial metrics are predictive of neoadjuvant ICB efficacy in breast cancer.

Published
2024

2. Characterizing the Tumor Immune Microenvironment with Tyramide-Based Multiplex Immunofluorescence.

Author

Mori, Hidetoshi, Bolen, Jennifer, Schuetter, Louis, Massion, Pierre, Hoyt, Clifford C, VandenBerg, Scott, Esserman, Laura, Borowsky, Alexander D, and Campbell, Michael J

Subjects
Breast cancer, Immune cells, Immunohistochemistry, Multiplex, Clinical Sciences, Oncology & Carcinogenesis
Abstract

Multiplex immunofluorescence (mIF) allows simultaneous antibody-based detection of multiple markers with a nuclear counterstain on a single tissue section. Recent studies have demonstrated that mIF is becoming an important tool for immune profiling the tumor microenvironment, further advancing our understanding of the interplay between cancer and the immune system, and identifying predictive biomarkers of response to immunotherapy. Expediting mIF discoveries is leading to improved diagnostic panels, whereas it is important that mIF protocols be standardized to facilitate their transition into clinical use. Manual processing of sections for mIF is time consuming and a potential source of variability across numerous samples. To increase reproducibility and throughput we demonstrate the use of an automated slide stainer for mIF incorporating tyramide signal amplification (TSA). We describe two panels aimed at characterizing the tumor immune microenvironment. Panel 1 included CD3, CD20, CD117, FOXP3, Ki67, pancytokeratins (CK), and DAPI, and Panel 2 included CD3, CD8, CD68, PD-1, PD-L1, CK, and DAPI. Primary antibodies were first tested by standard immunohistochemistry and single-plex IF, then multiplex panels were developed and images were obtained using a Vectra 3.0 multispectral imaging system. Various methods for image analysis (identifying cell types, determining cell densities, characterizing cell-cell associations) are outlined. These mIF protocols will be invaluable tools for immune profiling the tumor microenvironment.

Published
2020

11. Comparison of Biomarker Modalities for Predicting Response to PD-1/PD-L1 Checkpoint Blockade

Author

Lu, Steve, primary, Stein, Julie E., additional, Rimm, David L., additional, Wang, Daphne W., additional, Bell, J. Michael, additional, Johnson, Douglas B., additional, Sosman, Jeffrey A., additional, Schalper, Kurt A., additional, Anders, Robert A., additional, Wang, Hao, additional, Hoyt, Clifford, additional, Pardoll, Drew M., additional, Danilova, Ludmila, additional, and Taube, Janis M., additional

Published
2019
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12. Abstract LB-318: Multi-institutional TSA-amplified Multiplexed Immunofluorescence Reproducibility Evaluation (MITRE study): Reproducibility assessment of an automated multiplexed immunofluorescence slide staining, imaging, and analysis workflow

Author

Hoyt, Clifford, primary, Roman, Kristin, additional, Engle, Liz, additional, Wang, Chichung, additional, Ballesteros-Merino, Carmen, additional, Jensen, Shawn M., additional, McGuire, John, additional, Zheng, Yi, additional, Coltharp, Carla, additional, Jiang, Mei, additional, Lucas, Justin, additional, Parra, Edwin, additional, Wistuba, Ignacio, additional, Locke, Darren, additional, Fox, Bernard A., additional, Rimm, David L., additional, and Taube, Janis Marie, additional

Published
2019
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14. Automated Multiplex Immunofluorescence Panel for Immuno-oncology Studies on Formalin-fixed Carcinoma Tissue Specimens

Author

Surace, Michael, primary, DaCosta, Karma, primary, Huntley, Anna, primary, Zhao, Weiguang, primary, Bagnall, Christopher, primary, Brown, Charles, primary, Wang, Chichung, primary, Roman, Kristin, primary, Cann, Jennifer, primary, Lewis, Arthur, primary, Steele, Keith, primary, Rebelatto, Marlon, primary, Parra, Edwin R., primary, Hoyt, Clifford C., primary, and Rodriguez-Canales, Jaime, primary

Published
2019
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15. Merging spectroscopy and digital imaging enhances cell research

Author

Hoyt, Clifford C. and Benson, Douglas M.

Subjects
Image processing -- Digital techniques, Photoelectron spectroscopy -- Usage, Microscopy, Medical -- Innovations, Cell research -- Equipment and supplies, Business, Electronics and electrical industries, Engineering and manufacturing industries
Published
1992

16. Radiometry: attaining absolute accuracy in the 1990s

Author

Hoyt, Clifford C. and Zalewski, Edward

Subjects
Radiation -- Measurement, Radiometers -- Standards, Business, Electronics and electrical industries, Engineering and manufacturing industries
Published
1990

17. Multiparametric immune profiling in HPV– oral squamous cell cancer

Author

Feng, Zipei, primary, Bethmann, Daniel, additional, Kappler, Matthias, additional, Ballesteros-Merino, Carmen, additional, Eckert, Alexander, additional, Bell, R. Bryan, additional, Cheng, Allen, additional, Bui, Tuan, additional, Leidner, Rom, additional, Urba, Walter J., additional, Johnson, Kent, additional, Hoyt, Clifford, additional, Bifulco, Carlo B., additional, Bukur, Juergen, additional, Wickenhauser, Claudia, additional, Seliger, Barbara, additional, and Fox, Bernard A., additional

Published
2017
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18. Additional file 1: Figure S1. of Multispectral imaging of formalin-fixed tissue predicts ability to generate tumor-infiltrating lymphocytes from melanoma

Author

Zipei Feng, Puri, Sachin, Moudgil, Tarsem, Wood, William, Hoyt, Clifford, Chichung Wang, Urba, Walter, Curti, Brendan, Bifulco, Carlo, and Fox, Bernard

Abstract

Schematic representation of process for TIL initiation, expansion and testing. Figure S2. Lymphocytic immune infiltrate is insufficient to predict TIL culture success. A) Representative H&E stain from 4 patients, two are classified as 3+ (Top) and two are classified as 1+ (Bottom), TIL culture status is indicated above images. B) Compares average pathology scores of lymphocytic infiltrate between tumors that grew TILs and those that did not. Figure S3. Comparison of two methods to evaluate immune infiltrate. A) Comparison between % CD8 T cell infiltrate and # of CD8 positive cells/mm^2. B) Comparison between # of CD8 positive T cells/mm^2 determined using PerkinElmer and Definiens. The comparisons were done using the identical image. Statistics were determined using Prism. Figure S4. PD-L1 Localization. A) On tumor cells B) on CD8+ T cells and C) on CD163+ macrophages. Figure S5. Time of growth is predictive of tumor reactivity. Statistics were done using unpaired nonparametric T test. Significance was established at P < 0.05. Figure S6. Comparison between FFPE (Top) and frozen (Bottom) sections. A,F) CD8; B,G) CD3; C,H) CD163; D,I) FoxP3; E,J) PD-L1. Figure S7. Heatmap representation of parameters generated from multispectral imaging with dark red indicating maximal expression and dark blue indicating minimum expression. *indicates patients from whom we failed to culture TIL. **indicates tumor sample that grew TIL that were not reactive to autologous tumor. Figure S8. Multispectral image showing individual channels: Original is the raw image with all channels taken using the Vectra imaging software. The spectrum for each fluorophore is measured with control slides and subtracted from the original image to establish individual channels and the composite. Figure S9. Representative image from individual multispectral samples. TIL status is indicated with “+” or “-“. Enumerated immune infiltrates are indicated for each sample in the lower right corner. (PPTX 38563 kb)

Published
2015
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20. Toward higher res, lower cost quality color and multispectral imaging

Author

Hoyt, Clifford C.

Subjects
Image processing -- Digital techniques, Resolution (Optics) -- Research, Multispectral photography -- Research, Imaging systems -- Research, Liquid crystals -- Usage, Digital filters -- Usage, Business, Computers and office automation industries, Electronics and electrical industries
Published
1995

23. Abstract 5123: Multiplex in situ immunoprofiling and survival outcomes in non-small cell lung cancer

Author

Lin, Steven H., primary, Mansfield, James R., additional, Rao, Xiayu, additional, Jiang, Wen, additional, Fang, Penny, additional, Roman, Kristin, additional, Wang, Chichung, additional, Komaki, Ritsuko, additional, Hahn, Stephen, additional, Swisher, Stephen G., additional, Fujimoto, Junya, additional, Wistuba, Ignacio, additional, Wang, Jing, additional, and Hoyt, Clifford C., additional

Published
2016
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24. Biomarker quantification by multiplexed quantum dot technology for predicting lymph node metastasis and prognosis in head and neck cancer

Author

Hu, Zhongliang, primary, Qian, Guoqing, additional, Müller, Susan, additional, Xu, Jing, additional, Saba, Nabil F., additional, Kim, Sungjin, additional, Chen, Zhengjia, additional, Jiang, Ning, additional, Wang, Dongsheng, additional, Zhang, Hongzheng, additional, Lane, Kristin, additional, Hoyt, Clifford, additional, Shin, Dong M., additional, and Chen, Zhuo Georgia, additional

Published
2016
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26. Progressive loss of anti-HER2 CD4+ T-helper type 1 response in breast tumorigenesis and the potential for immune restoration

Author

Datta, Jashodeep, primary, Rosemblit, Cinthia, additional, Berk, Erik, additional, Showalter, Lori, additional, Namjoshi, Prachi, additional, Mick, Rosemarie, additional, Lee, Kathreen P, additional, Brod, Andrew M, additional, Yang, Rachel L, additional, Kelz, Rachel R, additional, Fitzpatrick, Elizabeth, additional, Hoyt, Clifford, additional, Feldman, Michael D, additional, Zhang, Paul J, additional, Xu, Shuwen, additional, Koski, Gary K, additional, and Czerniecki, Brian J, additional

Published
2015
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42. In Vivo Stable Tumor-Specific Painting in Various Colors Using Dehalogenase-Based Protein-Tag Fluorescent Ligands

Author

Kosaka, Nobuyuki, primary, Ogawa, Mikako, additional, Choyke, Peter L., additional, Karassina, Natasha, additional, Corona, Cesear, additional, McDougall, Mark, additional, Lynch, David T., additional, Hoyt, Clifford C., additional, Levenson, Richard M., additional, Los, Georgyi V., additional, and Kobayashi, Hisataka, additional

Published
2009
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45. Multispectral imaging of formalin-fixed tissue predicts ability to generate tumor-infiltrating lymphocytes from melanoma.

Author

Zipei Feng, Puri, Sachin, Moudgil, Tarsem, Wood, William, Hoyt, Clifford C., Chichung Wang, Urba, Walter J., Curti, Brendan D., Bifulco, Carlo B., and Fox, Bernard A.

Subjects
LYMPHOCYTES, MELANOMA, T cells, THERAPEUTICS
Abstract

Background: Adoptive T cell therapy (ACT) has shown great promise in melanoma, with over 50% response rate in patients where autologous tumor-reactive tumor-infiltrating lymphocytes (TIL) can be cultured and expanded. A major limitation of ACT is the inability to generate or expand autologous tumor-reactive TIL in 25-45% of patients tested. Methods that successfully identify tumors that are not suitable for TIL generation by standard methods would eliminate the costs of fruitless expansion and enable these patients to receive alternate therapy immediately. Methods: Multispectral fluorescent immunohistochemistry with a panel including CD3, CD8, FoxP3, CD163, PD-L1 was used to analyze the tumor microenvironment in 17 patients with melanoma among our 36-patient cohort to predict successful TIL generation. Additionally, we compared tumor fragments and enzymatic digestion of tumor samples for efficiency in generating tumor-reactive TIL. Results: Tumor-reactive TIL were generated from 21/36 (58%) of melanomas and for 12/13 (92%) tumors where both enzymatic and fragment methods were compared. TIL generation was successful in 10/13 enzymatic preparations and in 10/13 fragment cultures; combination of both methods resulted in successful generation of autologous tumor-reactive TIL in 12/13 patients. In 17 patients for whom tissue blocks were available, IHC analysis identified that while the presence of CD8+ T cells alone was insufficient to predict successful TIL generation, the CD8+ to FoxP3+ ratio was predictive with a positive-predictive value (PPV) of 91% and negative-predictive value (NPV) of 86%. Incorporation of CD163+ macrophage numbers and CD8:PD-L1 ratio did not improve the PPV. However, the NPV could be improved to 100% by including the ratio of CD8+:PD-L1+ expressing cells. Conclusion: This is the first study to apply 7-color multispectral immunohistochemistry to analyze the immune environment of tumors from patients with melanoma. Assessment of the data using unsupervised hierarchical clustering identified tumors from which we were unable to generate TIL. If substantiated, this immune profile could be applied to select patients for TIL generation. Additionally, this biomarker profile may also indicate a pre-existing immune response, and serve as a predictive biomarker of patients who will respond to checkpoint blockade. We postulate that expanding the spectrum of inhibitory cells and molecules assessed using this technique could guide combination immunotherapy treatments and improve response rates. [ABSTRACT FROM AUTHOR]

Published
2015
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