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2. High Community-Level Social Vulnerability is Associated with Worse Recurrence-Free Survival (RFS) After Resection of Extremity and Truncal Soft Tissue Sarcoma

Author

Traweek, Raymond S., Lyu, Heather G., Witt, Russell G., Snyder, Rebecca A., Nassif, Elise F., Krijgh, David D., Smith, Jeffrey M., Tilney, Gordon S., Feng, Chun, Chiang, Yi-Ju, Torres, Keila E., Roubaud, Margaret J., Scally, Christopher P., Hunt, Kelly K., Keung, Emily Z., Mericli, Alexander F., and Roland, Christina L.

Published
2024
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3. A randomized, non-comparative phase 2 study of neoadjuvant immune-checkpoint blockade in retroperitoneal dedifferentiated liposarcoma and extremity/truncal undifferentiated pleomorphic sarcoma

Author

Roland, Christina L., Nassif Haddad, Elise F., Keung, Emily Z., Wang, Wei-Lien, Lazar, Alexander J., Lin, Heather, Chelvanambi, Manoj, Parra, Edwin R., Wani, Khalida, Guadagnolo, B. Ashleigh, Bishop, Andrew J., Burton, Elizabeth M., Hunt, Kelly K., Torres, Keila E., Feig, Barry W., Scally, Christopher P., Lewis, Valerae O., Bird, Justin E., Ratan, Ravin, Araujo, Dejka, Zarzour, M. Alexandra, Patel, Shreyaskumar, Benjamin, Robert, Conley, Anthony P., Livingston, J. Andrew, Ravi, Vinod, Tawbi, Hussein A., Lin, Patrick P., Moon, Bryan S., Satcher, Robert L., Mujtaba, Bilal, Witt, Russell G., Traweek, Raymond S., Cope, Brandon, Lazcano, Rossana, Wu, Chia-Chin, Zhou, Xiao, Mohammad, Mohammad M., Chu, Randy A., Zhang, Jianhua, Damania, Ashish, Sahasrabhojane, Pranoti, Tate, Taylor, Callahan, Kate, Nguyen, Sa, Ingram, Davis, Morey, Rohini, Crosby, Shadarra, Mathew, Grace, Duncan, Sheila, Lima, Cibelle F., Blay, Jean-Yves, Fridman, Wolf Herman, Shaw, Kenna, Wistuba, Ignacio, Futreal, Andrew, Ajami, Nadim, Wargo, Jennifer A., and Somaiah, Neeta

Published
2024
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4. ASO Visual Abstract: Clinical Variables Influencing Outcomes in Patients with Atypical Intradermal Smooth Muscle Neoplasms (Formerly Cutaneous Leiomyosarcomas)—Single-Institution Study of 95 Surgical Patients

Author

Gingrich, Alicia, Wangsiricharoen, Sintawat, Torres, Madeline B., Ravi, Vinod, Ratan, Ravin, Keung, Emily Z., Scally, Christopher P., Lazar, Alexander J., Wang, Wei-Lien, Roland, Christina L., Hunt, Kelly K., Yu, Wendong, and Torres, Keila E.

Published
2024
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5. ASO Visual Abstract: High Community-Level Social Vulnerability is Associated with Worse Recurrence-Free Survival Following Resection of Extremity and Truncal Soft-Tissue Sarcoma

Author

Traweek, Raymond S., Lyu, Heather, Witt, Russell G., Snyder, Rebecca A., Nassif, Elise F., Krijgh, David D., Smith, Jeffrey M., Tilney, Gordon S., Feng, Chun, Chiang, Yi-Ju, Torres, Keila E., Roubaud, Margaret J., Scally, Christopher P., Hunt, Kelly K., Keung, Emily Z., Mericli, Alexander F., and Roland, Christina L.

Published
2024
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6. Practice Pattern Variability in the Management of Regional Lymph Node Metastasis in Extremity and Trunk Soft Tissue Sarcoma: A Survey of the Society of Surgical Oncology and Musculoskeletal Tumor Society Membership

Author

Witt, Russell G., Voss, Rachel K., Chiang, Yi-Ju, Nguyen, Sa, Scally, Christopher P., Lin, Patrick P., Torres, Keila E., Moon, Bryan S., Satcher, Robert L., Hunt, Kelly K., Bird, Justin E., Feig, Barry W., Lewis, Valerae O., Roland, Christina L., and Keung, Emily Z.

Published
2023
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8. SABR for Sarcoma Lung Metastases: Indications for Treatment and Guidance for Patient Selection

Author

Farooqi, Ahsan S., Yoder, Alison K., Lin, Heather Y., Pasalic, Dario, Erasmus, Jeremy, Betancourt, Sonia, Wernz, Cort, Mitra, Devarati, Zarzour, Maria A., Somaiah, Neeta, Conley, Anthony, Ratan, Ravin, Livingston, Andrew, Araujo, Dejka M., Roland, Christina, Scally, Christopher, Keung, Emily, Gandhi, Saumil N., Ashleigh Guadagnolo, B., Nguyen, Quynh-Nhu, and Bishop, Andrew J.

Published
2024
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12. Primary tumor site for localized Merkel cell carcinoma drives different management strategies without impacting oncologic outcomes

Author

Cass, Samuel, Cope, Brandon, Bishop, Andrew J., Chiang, Yi-Ju, Ashleigh Guadagnolo, B., Farooqi, Ahsan, Morrison, William, Witt, Russell G., Seervai, Riyad N.H., Garden, Adam S., Fuller, Clifton D., Goepfert, Ryan P., Ross, Merrick, Gershenwald, Jeffrey E., Wong, Michael, Aung, Phyu P., Keung, Emily Z., and Mitra, Devarati

Published
2023
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13. Neoadjuvant relatlimab and nivolumab in resectable melanoma

Author

Amaria, Rodabe N., Postow, Michael, Burton, Elizabeth M., Tezlaff, Michael T., Ross, Merrick I., Torres-Cabala, Carlos, Glitza, Isabella C., Duan, Fei, Milton, Denái R., Busam, Klaus, Simpson, Lauren, McQuade, Jennifer L., Wong, Michael K., Gershenwald, Jeffrey E., Lee, Jeffrey E., Goepfert, Ryan P., Keung, Emily Z., Fisher, Sarah B., Betof-Warner, Allison, Shoushtari, Alexander N., Callahan, Margaret, Coit, Daniel, Bartlett, Edmund K., Bello, Danielle, Momtaz, Parisa, Nicholas, Courtney, Gu, Aidi, Zhang, Xuejun, Korivi, Brinda Rao, Patnana, Madhavi, Patel, Sapna P., Diab, Adi, Lucci, Anthony, Prieto, Victor G., Davies, Michael A., Allison, James P., Sharma, Padmanee, Wargo, Jennifer A., Ariyan, Charlotte, and Tawbi, Hussein A.

Published
2022
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15. B cells and tertiary lymphoid structures promote immunotherapy response

Author

Helmink, Beth A, Reddy, Sangeetha M, Gao, Jianjun, Zhang, Shaojun, Basar, Rafet, Thakur, Rohit, Yizhak, Keren, Sade-Feldman, Moshe, Blando, Jorge, Han, Guangchun, Gopalakrishnan, Vancheswaran, Xi, Yuanxin, Zhao, Hao, Amaria, Rodabe N, Tawbi, Hussein A, Cogdill, Alex P, Liu, Wenbin, LeBleu, Valerie S, Kugeratski, Fernanda G, Patel, Sapna, Davies, Michael A, Hwu, Patrick, Lee, Jeffrey E, Gershenwald, Jeffrey E, Lucci, Anthony, Arora, Reetakshi, Woodman, Scott, Keung, Emily Z, Gaudreau, Pierre-Olivier, Reuben, Alexandre, Spencer, Christine N, Burton, Elizabeth M, Haydu, Lauren E, Lazar, Alexander J, Zapassodi, Roberta, Hudgens, Courtney W, Ledesma, Deborah A, Ong, SuFey, Bailey, Michael, Warren, Sarah, Rao, Disha, Krijgsman, Oscar, Rozeman, Elisa A, Peeper, Daniel, Blank, Christian U, Schumacher, Ton N, Butterfield, Lisa H, Zelazowska, Monika A, McBride, Kevin M, Kalluri, Raghu, Allison, James, Petitprez, Florent, Fridman, Wolf Herman, Sautès-Fridman, Catherine, Hacohen, Nir, Rezvani, Katayoun, Sharma, Padmanee, Tetzlaff, Michael T, Wang, Linghua, and Wargo, Jennifer A

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Immunology, Immunization, Cancer, Vaccine Related, Genetics, B-Lymphocytes, Biomarkers, Tumor, Carcinoma, Renal Cell, Cell Cycle Checkpoints, Clone Cells, Dendritic Cells, Follicular, Gene Expression Regulation, Neoplastic, Humans, Immunologic Memory, Immunotherapy, Mass Spectrometry, Melanoma, Neoplasm Metastasis, Phenotype, Prognosis, RNA-Seq, Receptors, Immunologic, Single-Cell Analysis, T-Lymphocytes, Tertiary Lymphoid Structures, Transcriptome, General Science & Technology
Abstract

Treatment with immune checkpoint blockade (ICB) has revolutionized cancer therapy. Until now, predictive biomarkers1-10 and strategies to augment clinical response have largely focused on the T cell compartment. However, other immune subsets may also contribute to anti-tumour immunity11-15, although these have been less well-studied in ICB treatment16. A previously conducted neoadjuvant ICB trial in patients with melanoma showed via targeted expression profiling17 that B cell signatures were enriched in the tumours of patients who respond to treatment versus non-responding patients. To build on this, here we performed bulk RNA sequencing and found that B cell markers were the most differentially expressed genes in the tumours of responders versus non-responders. Our findings were corroborated using a computational method (MCP-counter18) to estimate the immune and stromal composition in this and two other ICB-treated cohorts (patients with melanoma and renal cell carcinoma). Histological evaluation highlighted the localization of B cells within tertiary lymphoid structures. We assessed the potential functional contributions of B cells via bulk and single-cell RNA sequencing, which demonstrate clonal expansion and unique functional states of B cells in responders. Mass cytometry showed that switched memory B cells were enriched in the tumours of responders. Together, these data provide insights into the potential role of B cells and tertiary lymphoid structures in the response to ICB treatment, with implications for the development of biomarkers and therapeutic targets.

Published
2020

17. Retrospective Analysis of Retroperitoneal-Abdominal-Pelvic Ganglioneuromas: An International Study by the Transatlantic Australasian Retroperitoneal Sarcoma Working Group (TARPSWG)

Author

Noh, Sangkyu, Nessim, Carolyn, Keung, Emily Z., Roland, Christina L., Strauss, Dirk, Sivarajah, Gausihi, Fiore, Marco, Biasoni, Davide, Cioffi, Stefano Piero Bernardo, Mehtsun, Winta, Cananzi, Ferdinando Carlo Maria, Sicoli, Federico, Quagliuolo, Vittorio, Chen, Jun, Luo, Chenghua, Gladdy, Rebecca A., Swallow, Carol, Johnston, Wendy, Ford, Samuel J., Evenden, Caroline, Tirotta, Fabio, Almond, Max, Nguyen, Laura, Rutkowski, Piotr, Krotewicz, Maria, Pennacchioli, Elisabetta, Cardona, Kenneth, Gamboa, Adriana, Hompes, Daphne, Renard, Marleen, Kollár, Attila, Ryser, Christoph O., Vassos, Nikolaos, Raut, Chandrajit P., Fairweather, Mark, Krakorova, Dagmar Adamkova, Quildrian, Sergio, Perhavec, Andraz, Nizri, Eran, Farma, Jeffrey M., Greco, Stephanie H., Vincenzi, Bruno, Lopez, José Antonio González, Solerdecoll, Mireia Solans, Iwata, Shintaro, Fukushima, Suguru, Kim, Teresa, Tolomeo, Francesco, Snow, Hayden, Howlett-Jansen, Ynez, Tzanis, Dimitri, Nikulin, Maxim, Gronchi, Alessandro, and Sicklick, Jason K.

Published
2023
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18. Androgen receptor blockade promotes response to BRAF/MEK-targeted therapy

Author

Vellano, Christopher P., White, Michael G., Andrews, Miles C., Chelvanambi, Manoj, Witt, Russell G., Daniele, Joseph R., Titus, Mark, McQuade, Jennifer L., Conforti, Fabio, Burton, Elizabeth M., Lastrapes, Matthew J., Ologun, Gabriel, Cogdill, Alexandria P., Morad, Golnaz, Prieto, Peter, Lazar, Alexander J., Chu, Yanshuo, Han, Guangchun, Khan, M. A. Wadud, Helmink, Beth, Davies, Michael A., Amaria, Rodabe N., Kovacs, Jeffrey J., Woodman, Scott E., Patel, Sapna, Hwu, Patrick, Peoples, Michael, Lee, Jeffrey E., Cooper, Zachary A., Zhu, Haifeng, Gao, Guang, Banerjee, Hiya, Lau, Mike, Gershenwald, Jeffrey E., Lucci, Anthony, Keung, Emily Z., Ross, Merrick I., Pala, Laura, Pagan, Eleonora, Segura, Rossana Lazcano, Liu, Qian, Borthwick, Mikayla S., Lau, Eric, Yates, Melinda S., Westin, Shannon N., Wani, Khalida, Tetzlaff, Michael T., Haydu, Lauren E., Mahendra, Mikhila, Ma, XiaoYan, Logothetis, Christopher, Kulstad, Zachary, Johnson, Sarah, Hudgens, Courtney W., Feng, Ningping, Federico, Lorenzo, Long, Georgina V., Futreal, P. Andrew, Arur, Swathi, Tawbi, Hussein A., Moran, Amy E., Wang, Linghua, Heffernan, Timothy P., Marszalek, Joseph R., and Wargo, Jennifer A.

Published
2022
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19. Hypofractionated, 3-week, preoperative radiotherapy for patients with soft tissue sarcomas (HYPORT-STS): a single-centre, open-label, single-arm, phase 2 trial

Author

Guadagnolo, B Ashleigh, Bassett, Roland L, Mitra, Devarati, Farooqi, Ahsan, Hempel, Caroline, Dorber, Courtney, Willis, Tiara, Wang, Wei-Lien, Ratan, Ravin, Somaiah, Neeta, Benjamin, Robert S, Torres, Keila E, Hunt, Kelly K, Scally, Christopher P, Keung, Emily Z, Satcher, Robert L, Bird, Justin E, Lin, Patrick P, Moon, Bryan S, Lewis, Valerae O, Roland, Christina L, and Bishop, Andrew J

Published
2022
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20. ASO Visual Abstract: Practice Pattern Variability in the Management of Regional Lymph Node Metastasis in Extremity and Trunk Soft Tissue Sarcoma (ETSTS): A Survey of the Society of Surgical Oncology (SSO) and Musculoskeletal Tumor Society (MSTS) Membership

Author

Witt, Russell G., Voss, Rachel K., Chiang, Yi-Ju, Nguyen, Sa, Scally, Christopher P., Lin, Patrick P., Torres, Keila E., Moon, Bryan S., Satcher, Robert L., Hunt, Kelly K., Bird, Justin E., Feig, Barry W., Lewis, Valerae O., Roland, Christina L., and Keung, Emily Z.

Published
2023
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26. ASO Visual Abstract: Sentinel Lymph Node Biopsy for Extremity and Truncal Soft Tissue Sarcomas—A Systematic Review of the Literature

Author

Keung, Emily Z., Krause, Kate J., Maxwell, Jessica, Morris, Carol D., Crago, Aimee M., Houdek, Matthew T., Kane, John, Lewis, Valerae, Callegaro, Dario, Miller, Benjamin, Lazar, Alexander J., Gladdy, Rebecca, Raut, Chandrajit P., Fabbri, Nicola, Al-Refaie, Waddah, Fairweather, Mark, Wong, Sandra L., and Roland, Christina L.

Published
2023
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28. Safety and efficacy of percutaneous image‐guided ablation for soft tissue sarcoma metastases to the liver.

Author

Awad, Ahmed, Pal, Koustav, Yevich, Steven, Kuban, Joshua D., Tam, Alda, Odisio, Bruno C., Gupta, Sanjay, Habibollahi, Peiman, Bishop, Andrew J., Conley, Anthony Paul, Somaiah, Neeta, Araujo, Dejka M., Zarzour, Maria Alejandra, Ratan, Ravin, Roland, Christina L., Keung, Emily Z., Huang, Steven Y., and Sheth, Rahul A.

Subjects
SARCOMA, GASTROINTESTINAL stromal tumors, TREATMENT effectiveness, PROGRESSION-free survival, OVERALL survival, GUIDED tissue regeneration, LEIOMYOSARCOMA
Abstract

Purpose: To evaluate outcomes following percutaneous image‐guided ablation of soft tissue sarcoma metastases to the liver. Materials and Methods: A single‐institution retrospective analysis of patients with a diagnosis of metastatic soft tissue sarcoma who underwent percutaneous image‐guided ablation of hepatic metastases between January 2011 and December 2021 was performed. Patients with less than 60 days of follow‐up after ablation were excluded. The primary outcome was local tumor progression‐free survival (LPFS). Secondary outcomes included overall survival, liver‐specific progression‐free survival. and chemotherapy‐free survival. Results: Fifty‐five patients who underwent percutaneous ablation for 84 metastatic liver lesions were included. The most common histopathological subtypes were leiomyosarcoma (23/55), followed by gastrointestinal stromal tumor (22/55). The median treated liver lesions was 2 (range, 1–8), whereas the median size of metastases were 1.8 cm (0.3–8.7 cm). Complete response at 2 months was achieved in 90.5% of the treated lesions. LPFS was 83% at 1 year and 80% at 2 years. Liver‐specific progression‐free survival was 66% at 1 year and 40% at 2 years. The overall survival at 1 and 2 years was 98% and 94%. The chemotherapy‐free holiday from the start of ablation was 71.2% at 12 months. The complication rate was 3.6% (2/55); one of the complications was Common Terminology Criteria for Adverse Events grade 3 or higher. LPFS subgroup analysis for leiomyosarcoma versus gastrointestinal stromal tumor suggests histology‐agnostic outcomes (2 years, 89% vs 82%, p =.35). Conclusion: Percutaneous image‐guided liver ablation of soft tissue sarcoma metastases is safe and efficacious. Image‐guided ablation of sarcoma metastasis is a promising modality for treating sarcoma metastases to the liver, with a local tumor progression‐free survival of 83% and 80% at 1 and 2 years. Subgroup analysis demonstrated no significant differences between the local tumor progression‐free survival of gastrointestinal stromal tumor versus leiomyosarcoma, suggesting a histology‐agnostic treatment paradigm. [ABSTRACT FROM AUTHOR]

Published
2024
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29. Neoadjuvant Systemic Therapy for High-Risk Melanoma Patients

Author

Keung, Emily Z., Amaria, Rodabe N., Sondak, Vernon K., Ross, Merrick I., Kirkwood, John M., Wargo, Jennifer A., Balch, Charles M., editor, Atkins, Michael B., editor, Garbe, Claus, editor, Gershenwald, Jeffrey E., editor, Halpern, Allan C., editor, Kirkwood, John M., editor, McArthur, Grant A., editor, Thompson, John F., editor, and Sober, Arthur J., editor

Published
2020
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30. Melanoma Prognosis and Staging

Author

Keung, Emily Z., Balch, Charles M., Thompson, John F., Kirkwood, John M., Scolyer, Richard A., Sondak, Vernon K., Gershenwald, Jeffrey E., Balch, Charles M., editor, Atkins, Michael B., editor, Garbe, Claus, editor, Gershenwald, Jeffrey E., editor, Halpern, Allan C., editor, Kirkwood, John M., editor, McArthur, Grant A., editor, Thompson, John F., editor, and Sober, Arthur J., editor

Published
2020
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32. Enhancer reprogramming in PRC2-deficient malignant peripheral nerve sheath tumors induces a targetable de-differentiated state

Author

Kochat, Veena, Raman, Ayush T., Landers, Sharon M., Tang, Ming, Schulz, Jonathan, Terranova, Christopher, Landry, Jace P., Bhalla, Angela D., Beird, Hannah C., Wu, Chia-Chin, Jiang, Yingda, Mao, Xizeng, Lazcano, Rossana, Gite, Swati, Ingram, Davis R., Yi, Min, Zhang, Jianhua, Keung, Emily Z., Scally, Christopher P., Roland, Christina L., Hunt, Kelly K., Feig, Barry W., Futreal, P. Andrew, Hwu, Patrick, Wang, Wei-Lien, Lazar, Alexander J., Slopis, John M., Wilson-Robles, Heather, Wiener, Dominique J., McCutcheon, Ian E., Wustefeld-Janssens, Brandan, Rai, Kunal, and Torres, Keila E.

Published
2021
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36. Author Correction: Neoadjuvant relatlimab and nivolumab in resectable melanoma

Author

Amaria, Rodabe N., Postow, Michael, Burton, Elizabeth M., Tetzlaff, Michael T., Ross, Merrick I., Torres-Cabala, Carlos, Glitza, Isabella C., Duan, Fei, Milton, Denái R., Busam, Klaus, Simpson, Lauren, McQuade, Jennifer L., Wong, Michael K., Gershenwald, Jeffrey E., Lee, Jeffrey E., Goepfert, Ryan P., Keung, Emily Z., Fisher, Sarah B., Betof-Warner, Allison, Shoushtari, Alexander N., Callahan, Margaret, Coit, Daniel, Bartlett, Edmund K., Bello, Danielle, Momtaz, Parisa, Nicholas, Courtney, Gu, Aidi, Zhang, Xuejun, Korivi, Brinda Rao, Patnana, Madhavi, Patel, Sapna P., Diab, Adi, Lucci, Anthony, Prieto, Victor G., Davies, Michael A., Allison, James P., Sharma, Padmanee, Wargo, Jennifer A., Ariyan, Charlotte, and Tawbi, Hussein A.

Published
2023
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37. Author Correction: Androgen receptor blockade promotes response to BRAF/MEK-targeted therapy

Author

Vellano, Christopher P., White, Michael G., Andrews, Miles C., Chelvanambi, Manoj, Witt, Russell G., Daniele, Joseph R., Titus, Mark, McQuade, Jennifer L., Conforti, Fabio, Burton, Elizabeth M., Lastrapes, Matthew J., Ologun, Gabriel, Cogdill, Alexandria P., Morad, Golnaz, Prieto, Peter, Lazar, Alexander J., Chu, Yanshuo, Han, Guangchun, Khan, M. A. Wadud, Helmink, Beth, Davies, Michael A., Amaria, Rodabe N., Kovacs, Jeffrey J., Woodman, Scott E., Patel, Sapna, Hwu, Patrick, Peoples, Michael, Lee, Jeffrey E., Cooper, Zachary A., Zhu, Haifeng, Gao, Guang, Banerjee, Hiya, Lau, Mike, Gershenwald, Jeffrey E., Lucci, Anthony, Keung, Emily Z., Ross, Merrick I., Pala, Laura, Pagan, Eleonora, Segura, Rossana Lazcano, Liu, Qian, Borthwick, Mikayla S., Lau, Eric, Yates, Melinda S., Westin, Shannon N., Wani, Khalida, Tetzlaff, Michael T., Haydu, Lauren E., Mahendra, Mikhila, Ma, XiaoYan, Logothetis, Christopher, Kulstad, Zachary, Johnson, Sarah, Hudgens, Courtney W., Feng, Ningping, Federico, Lorenzo, Long, Georgina V., Futreal, P. Andrew, Arur, Swathi, Tawbi, Hussein A., Moran, Amy E., Wang, Linghua, Heffernan, Timothy P., Marszalek, Joseph R., and Wargo, Jennifer A.

Published
2023
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39. Systematic Epigenomic Analysis Reveals Chromatin States Associated with Melanoma Progression

Author

Fiziev, Petko, Akdemir, Kadir C, Miller, John P, Keung, Emily Z, Samant, Neha S, Sharma, Sneha, Natale, Christopher A, Terranova, Christopher J, Maitituoheti, Mayinuer, Amin, Samirkumar B, Martinez-Ledesma, Emmanuel, Dhamdhere, Mayura, Axelrad, Jacob B, Shah, Amiksha, Cheng, Christine S, Mahadeshwar, Harshad, Seth, Sahil, Barton, Michelle C, Protopopov, Alexei, Tsai, Kenneth Y, Davies, Michael A, Garcia, Benjamin A, Amit, Ido, Chin, Lynda, Ernst, Jason, and Rai, Kunal

Subjects
Biological Sciences, Human Genome, Cancer, Genetics, Aetiology, 2.1 Biological and endogenous factors, Acetylation, Cell Line, Cell Proliferation, Chromatin, Chromatin Immunoprecipitation, Disease-Free Survival, Epigenomics, Histone Deacetylase Inhibitors, Histone Deacetylases, Histones, Humans, Hydroxamic Acids, Kaplan-Meier Estimate, Melanoma, PTEN Phosphohydrolase, Principal Component Analysis, RNA Interference, RNA, Small Interfering, Signal Transduction, Vorinostat, CBP, ChIP-seq, DUSP5, HDAC, chromatin state, epigenome, histone modifications, melanoma, Biochemistry and Cell Biology, Medical Physiology, Biological sciences
Abstract

The extent and nature of epigenomic changes associated with melanoma progression is poorly understood. Through systematic epigenomic profiling of 35 epigenetic modifications and transcriptomic analysis, we define chromatin state changes associated with melanomagenesis by using a cell phenotypic model of non-tumorigenic and tumorigenic states. Computation of specific chromatin state transitions showed loss of histone acetylations and H3K4me2/3 on regulatory regions proximal to specific cancer-regulatory genes in important melanoma-driving cell signaling pathways. Importantly, such acetylation changes were also observed between benign nevi and malignant melanoma human tissues. Intriguingly, only a small fraction of chromatin state transitions correlated with expected changes in gene expression patterns. Restoration of acetylation levels on deacetylated loci by histone deacetylase (HDAC) inhibitors selectively blocked excessive proliferation in tumorigenic cells and human melanoma cells, suggesting functional roles of observed chromatin state transitions in driving hyperproliferative phenotype. Through these results, we define functionally relevant chromatin states associated with melanoma progression.

Published
2017

42. High-Grade Pleomorphic Sarcomas Treated with Immune Checkpoint Blockade: The MD Anderson Cancer Center Experience.

Author

Nasr, Lewis F., Zoghbi, Marianne, Lazcano, Rossana, Nakazawa, Michael, Bishop, Andrew J., Farooqi, Ahsan, Mitra, Devarati, Guadagnolo, Beverly Ashleigh, Benjamin, Robert, Patel, Shreyaskumar, Ravi, Vinod, Araujo, Dejka M., Livingston, Andrew, Zarzour, Maria A., Conley, Anthony P., Ratan, Ravin, Somaiah, Neeta, Lazar, Alexander J., Roland, Christina, and Keung, Emily Z.

Subjects
CANCER treatment, SARCOMA, PATIENT safety, MICROMETASTASIS, SCIENTIFIC observation, IMMUNOTHERAPY, PROGRAMMED death-ligand 1, RETROSPECTIVE studies, CANCER patients, DESCRIPTIVE statistics, IMMUNE checkpoint inhibitors, DRUG approval, LONGITUDINAL method, DRUG efficacy, PROGRESSION-free survival, SPECIALTY hospitals, OVERALL survival, EVALUATION, CHEMICAL inhibitors
Abstract

Simple Summary: Undifferentiated pleomorphic sarcomas (UPSs) represent 10–20% of all soft tissue sarcomas (STSs) and have quickly emerged as one of the more immune-sensitive types. There are few real-world data on the use of immune checkpoint blockade (ICB) in UPS patients and those with other high-grade pleomorphic STSs. This is a retrospective, observational study of all patients with metastatic high-grade pleomorphic sarcomas treated with FDA-approved ICB at MD Anderson Cancer Center intended to describe the efficacy and toxicity of ICB in this particular group of patients. We find that our outcomes are comparable to those in the published literature and pose a question regarding the need to further evaluate the optimal sequencing of radiotherapy and prior lines of systemic therapy. Background: Undifferentiated pleomorphic sarcomas (UPSs) are amongst the most common subtypes of soft-tissue sarcomas. Few real-world data on the use of immune checkpoint blockade (ICB) in UPS patients and other high-grade pleomorphic STS patients are available. Purpose: The purpose of our study is to describe the efficacy and toxicity of ICB in patients with advanced UPSs and other high-grade pleomorphic sarcomas treated at our institution. Methods: This is a retrospective, observational study of all patients with metastatic high-grade pleomorphic sarcomas treated with FDA-approved ICB at MD Anderson Cancer Center between 1 January 2015 and 1 January 2023. Patients included in trials for which results are not yet published were excluded. Results: Thirty-six patients with advanced/metastatic pleomorphic sarcomas were included. The median age was 52 years. A total of 26 patients (72%) had UPSs and 10 patients (28%) had other high-grade pleomorphic sarcomas. The median follow-up time was 8.8 months. The median PFS was 2.9 months. The 3-month PFS and 6-month PFS were 46% and 32%, respectively. The median OS was 12.9 months. The 12-month OS and 24-month OS were 53% and 29%, respectively. The best response, previous RT, and type of ICB treatment were significantly and independently associated with shorter PFS (p = 0.0012, p = 0.0019 and p = 0.036, respectively). No new safety signal was identified, and the toxicity was overall manageable with no toxic deaths and only four patients (11%) stopping treatment due to toxicity. Conclusions: Real-world retrospective data are consistent with the published literature, with a promising 6-month PFS of 32%. Partial or stable responders to ICB treatment have significantly improved PFS compared to progressors. [ABSTRACT FROM AUTHOR]

Published
2024
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45. Dual Roles of RNF2 in Melanoma Progression

Author

Rai, Kunal, Akdemir, Kadir C, Kwong, Lawrence N, Fiziev, Petko, Wu, Chang-Jiun, Keung, Emily Z, Sharma, Sneha, Samant, Neha S, Williams, Maura, Axelrad, Jacob B, Shah, Amiksha, Yang, Dong, Grimm, Elizabeth A, Barton, Michelle C, Milton, Denai R, Heffernan, Timothy P, Horner, James W, Ekmekcioglu, Suhendan, Lazar, Alexander J, Ernst, Jason, and Chin, Lynda

Subjects
Biochemistry and Cell Biology, Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Biological Sciences, Genetics, Biotechnology, Cancer, 1.1 Normal biological development and functioning, Underpinning research, 2.1 Biological and endogenous factors, Aetiology, Animals, Catalysis, Cell Transformation, Neoplastic, Cyclin D2, Disease Progression, E1A-Associated p300 Protein, Gene Expression, Gene Expression Regulation, Neoplastic, Histone Demethylases, Humans, Latent TGF-beta Binding Proteins, MAP Kinase Signaling System, Melanoma, Mice, Neoplasm Metastasis, Nuclear Proteins, Oncogenes, Phosphorylation, Polycomb Repressive Complex 1, Prognosis, Promoter Regions, Genetic, Transforming Growth Factor beta, Biochemistry and cell biology, Oncology and carcinogenesis
Abstract

UnlabelledEpigenetic regulators have emerged as critical factors governing the biology of cancer. Here, in the context of melanoma, we show that RNF2 is prognostic, exhibiting progression-correlated expression in human melanocytic neoplasms. Through a series of complementary gain-of-function and loss-of-function studies in mouse and human systems, we establish that RNF2 is oncogenic and prometastatic. Mechanistically, RNF2-mediated invasive behavior is dependent on its ability to monoubiquitinate H2AK119 at the promoter of LTBP2, resulting in silencing of this negative regulator of TGFβ signaling. In contrast, RNF2's oncogenic activity does not require its catalytic activity nor does it derive from its canonical gene repression function. Instead, RNF2 drives proliferation through direct transcriptional upregulation of the cell-cycle regulator CCND2. We further show that MEK1-mediated phosphorylation of RNF2 promotes recruitment of activating histone modifiers UTX and p300 to a subset of poised promoters, which activates gene expression. In summary, RNF2 regulates distinct biologic processes in the genesis and progression of melanoma via different molecular mechanisms.SignificanceThe role of epigenetic regulators in cancer progression is being increasingly appreciated. We show novel roles for RNF2 in melanoma tumorigenesis and metastasis, albeit via different mechanisms. Our findings support the notion that epigenetic regulators, such as RNF2, directly and functionally control powerful gene networks that are vital in multiple cancer processes.

Published
2015

46. B cells are associated with survival and immunotherapy response in sarcoma

Author

Petitprez, Florent, de Reyniès, Aurélien, Keung, Emily Z., Chen, Tom Wei-Wu, Sun, Cheng-Ming, Calderaro, Julien, and Jeng, Yung-Ming

Subjects
Sarcoma -- Care and treatment -- Patient outcomes, Immunotherapy -- Patient outcomes, B cells -- Physiological aspects, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Soft-tissue sarcomas represent a heterogeneous group of cancer, with more than 50 histological subtypes.sup.1,2. The clinical presentation of patients with different subtypes is often atypical, and responses to therapies such as immune checkpoint blockade vary widely.sup.3,4. To explain this clinical variability, here we study gene expression profiles in 608 tumours across subtypes of soft-tissue sarcoma. We establish an immune-based classification on the basis of the composition of the tumour microenvironment and identify five distinct phenotypes: immune-low (A and B), immune-high (D and E), and highly vascularized (C) groups. In situ analysis of an independent validation cohort shows that class E was characterized by the presence of tertiary lymphoid structures that contain T cells and follicular dendritic cells and are particularly rich in B cells. B cells are the strongest prognostic factor even in the context of high or low CD8.sup.+ T cells and cytotoxic contents. The class-E group demonstrated improved survival and a high response rate to PD1 blockade with pembrolizumab in a phase 2 clinical trial. Together, this work confirms the immune subtypes in patients with soft-tissue sarcoma, and unravels the potential of B-cell-rich tertiary lymphoid structures to guide clinical decision-making and treatments, which could have broader applications in other diseases. Immune profiling of the tumour microenvironment of soft-tissue sarcoma identifies a group of patients with high levels of B-cell infiltration and tertiary lymphoid structures that have improved survival and a high response rate to immune checkpoint blockade therapy., Author(s): Florent Petitprez [sup.1] [sup.2] [sup.3] [sup.4] , Aurélien de Reyniès [sup.4] , Emily Z. Keung [sup.5] , Tom Wei-Wu Chen [sup.6] [sup.7] [sup.8] [sup.9] , Cheng-Ming Sun [sup.1] [sup.2] [...]

Published
2020
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48. The Future of Targeted Therapy for Leiomyosarcoma.

Author

Denu, Ryan A., Dann, Amanda M., Keung, Emily Z., Nakazawa, Michael S., and Nassif Haddad, Elise F.

Subjects
MACROPHAGES, LEIOMYOSARCOMA, CELL physiology, EPIGENOMICS, IMMUNOTHERAPY, GENE expression profiling, DNA damage, TELOMERES, INDIVIDUALIZED medicine
Abstract

Simple Summary: Leiomyosarcoma is a subtype of soft tissue sarcoma with poor outcomes and response to currently available treatments. The goal of this review is to assess the current landscape of targeted therapies and explore how our current understanding of the biology of leiomyosarcoma may inform the development of new targeted therapies to improve the treatment of leiomyosarcoma. Leiomyosarcoma (LMS) is an aggressive subtype of soft tissue sarcoma that arises from smooth muscle cells, most commonly in the uterus and retroperitoneum. LMS is a heterogeneous disease with diverse clinical and molecular characteristics that have yet to be fully understood. Molecular profiling has uncovered possible targets amenable to treatment, though this has yet to translate into approved targeted therapies in LMS. This review will explore historic and recent findings from molecular profiling, highlight promising avenues of current investigation, and suggest possible future strategies to move toward the goal of molecularly matched treatment of LMS. We focus on targeting the DNA damage response, the macrophage-rich micro-environment, the PI3K/mTOR pathway, epigenetic regulators, and telomere biology. [ABSTRACT FROM AUTHOR]

Published
2024
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49. The interplay between neoantigens and immune cells in sarcomas treated with checkpoint inhibition

Author

Anzar, Irantzu, primary, Malone, Brandon, additional, Samarakoon, Pubudu, additional, Vardaxis, Ioannis, additional, Simovski, Boris, additional, Fontenelle, Hugues, additional, Meza-Zepeda, Leonardo A., additional, Stratford, Richard, additional, Keung, Emily Z., additional, Burgess, Melissa, additional, Tawbi, Hussein A., additional, Myklebost, Ola, additional, and Clancy, Trevor, additional

Published
2023
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