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1. Figure S9 from Circulating and Intratumoral Immune Determinants of Response to Atezolizumab plus Bevacizumab in Patients with Variant Histology or Sarcomatoid Renal Cell Carcinoma

Author

Saliby, Renee Maria, primary, El Zarif, Talal, primary, Bakouny, Ziad, primary, Shah, Valisha, primary, Xie, Wanling, primary, Flippot, Ronan, primary, Denize, Thomas, primary, Kane, M. Harry, primary, Madsen, Katrine N., primary, Ficial, Miriam, primary, Hirsch, Laure, primary, Wei, Xiao X., primary, Steinharter, John A., primary, Harshman, Lauren C., primary, Vaishampayan, Ulka N., primary, Severgnini, Mariano, primary, McDermott, David F., primary, Lee, Gwo-Shu Mary, primary, Xu, Wenxin, primary, Van Allen, Eliezer M., primary, McGregor, Bradley A., primary, Signoretti, Sabina, primary, Choueiri, Toni K., primary, McKay, Rana R., primary, and Braun, David A., primary

Published
2023
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2. Table S1 from Circulating and Intratumoral Immune Determinants of Response to Atezolizumab plus Bevacizumab in Patients with Variant Histology or Sarcomatoid Renal Cell Carcinoma

Author

Saliby, Renee Maria, primary, El Zarif, Talal, primary, Bakouny, Ziad, primary, Shah, Valisha, primary, Xie, Wanling, primary, Flippot, Ronan, primary, Denize, Thomas, primary, Kane, M. Harry, primary, Madsen, Katrine N., primary, Ficial, Miriam, primary, Hirsch, Laure, primary, Wei, Xiao X., primary, Steinharter, John A., primary, Harshman, Lauren C., primary, Vaishampayan, Ulka N., primary, Severgnini, Mariano, primary, McDermott, David F., primary, Lee, Gwo-Shu Mary, primary, Xu, Wenxin, primary, Van Allen, Eliezer M., primary, McGregor, Bradley A., primary, Signoretti, Sabina, primary, Choueiri, Toni K., primary, McKay, Rana R., primary, and Braun, David A., primary

Published
2023
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3. Supplementary Data from Circulating and Intratumoral Immune Determinants of Response to Atezolizumab plus Bevacizumab in Patients with Variant Histology or Sarcomatoid Renal Cell Carcinoma

Author

Saliby, Renee Maria, primary, El Zarif, Talal, primary, Bakouny, Ziad, primary, Shah, Valisha, primary, Xie, Wanling, primary, Flippot, Ronan, primary, Denize, Thomas, primary, Kane, M. Harry, primary, Madsen, Katrine N., primary, Ficial, Miriam, primary, Hirsch, Laure, primary, Wei, Xiao X., primary, Steinharter, John A., primary, Harshman, Lauren C., primary, Vaishampayan, Ulka N., primary, Severgnini, Mariano, primary, McDermott, David F., primary, Lee, Gwo-Shu Mary, primary, Xu, Wenxin, primary, Van Allen, Eliezer M., primary, McGregor, Bradley A., primary, Signoretti, Sabina, primary, Choueiri, Toni K., primary, McKay, Rana R., primary, and Braun, David A., primary

Published
2023
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4. Data from Circulating and Intratumoral Immune Determinants of Response to Atezolizumab plus Bevacizumab in Patients with Variant Histology or Sarcomatoid Renal Cell Carcinoma

Author

Saliby, Renee Maria, primary, El Zarif, Talal, primary, Bakouny, Ziad, primary, Shah, Valisha, primary, Xie, Wanling, primary, Flippot, Ronan, primary, Denize, Thomas, primary, Kane, M. Harry, primary, Madsen, Katrine N., primary, Ficial, Miriam, primary, Hirsch, Laure, primary, Wei, Xiao X., primary, Steinharter, John A., primary, Harshman, Lauren C., primary, Vaishampayan, Ulka N., primary, Severgnini, Mariano, primary, McDermott, David F., primary, Lee, Gwo-Shu Mary, primary, Xu, Wenxin, primary, Van Allen, Eliezer M., primary, McGregor, Bradley A., primary, Signoretti, Sabina, primary, Choueiri, Toni K., primary, McKay, Rana R., primary, and Braun, David A., primary

Published
2023
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5. Impact of renal cell carcinoma molecular subtypes on immunotherapy and targeted therapy outcomes

Author

Saliby, Renée Maria, Labaki, Chris, Jammihal, Tejas R., Xie, Wanling, Sun, Maxine, Shah, Valisha, Saad, Eddy, Kane, M. Harry, Kashima, Soki, Sadak, Katherine, El Zarif, Talal, Poduval, Deepak, Motzer, Robert J., Powles, Thomas, Rini, Brian I., Albiges, Laurence, Pal, Sumanta K., McGregor, Bradley A., McKay, Rana R., Signoretti, Sabina, Van Allen, Eliezer M., Shukla, Sachet A., Choueiri, Toni K., and Braun, David A.

Published
2024
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6. Circulating and Intratumoral Immune Determinants of Response to Atezolizumab plus Bevacizumab in Patients with Variant Histology or Sarcomatoid Renal Cell Carcinoma

Author

Saliby, Renee Maria, primary, El Zarif, Talal, additional, Bakouny, Ziad, additional, Shah, Valisha, additional, Xie, Wanling, additional, Flippot, Ronan, additional, Denize, Thomas, additional, Kane, M. Harry, additional, Madsen, Katrine N., additional, Ficial, Miriam, additional, Hirsch, Laure, additional, Wei, Xiao X., additional, Steinharter, John A., additional, Harshman, Lauren C., additional, Vaishampayan, Ulka N., additional, Severgnini, Mariano, additional, McDermott, David F., additional, Lee, Gwo-Shu Mary, additional, Xu, Wenxin, additional, Van Allen, Eliezer M., additional, McGregor, Bradley A., additional, Signoretti, Sabina, additional, Choueiri, Toni K., additional, McKay, Rana R., additional, and Braun, David A., additional

Published
2023
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7. Proteogenomic Landscape of Breast Cancer Tumorigenesis and Targeted Therapy

Author

Krug, Karsten, Jaehnig, Eric J., Satpathy, Shankha, Blumenberg, Lili, Karpova, Alla, Anurag, Meenakshi, Miles, George, Mertins, Philipp, Geffen, Yifat, Tang, Lauren C., Heiman, David I., Cao, Song, Maruvka, Yosef E., Lei, Jonathan T., Huang, Chen, Kothadia, Ramani B., Colaprico, Antonio, Birger, Chet, Wang, Jarey, Dou, Yongchao, Wen, Bo, Shi, Zhiao, Liao, Yuxing, Wiznerowicz, Maciej, Wyczalkowski, Matthew A., Chen, Xi Steven, Kennedy, Jacob J., Paulovich, Amanda G., Thiagarajan, Mathangi, Kinsinger, Christopher R., Hiltke, Tara, Boja, Emily S., Mesri, Mehdi, Robles, Ana I., Rodriguez, Henry, Westbrook, Thomas F., Ding, Li, Getz, Gad, Clauser, Karl R., Fenyö, David, Ruggles, Kelly V., Zhang, Bing, Mani, D.R., Carr, Steven A., Ellis, Matthew J., Gillette, Michael A., Avanessian, Shayan C., Cai, Shuang, Chan, Daniel, Chen, Xian, Edwards, Nathan J., Hoofnagle, Andrew N., Kane, M. Harry, Ketchum, Karen A., Kuhn, Eric, Levine, Douglas A., Li, Shunqiang, Liebler, Daniel C., Liu, Tao, Luo, Jingqin, Madhavan, Subha, Maher, Chris, McDermott, Jason E., McGarvey, Peter B., Oberti, Mauricio, Pandey, Akhilesh, Payne, Samuel H., Ransohoff, David F., Rivers, Robert C., Rodland, Karin D., Rudnick, Paul, Sanders, Melinda E., Shaw, Kenna M., Shih, Ie-Ming, Slebos, Robbert J.C., Smith, Richard D., Snyder, Michael, Stein, Stephen E., Tabb, David L., Thangudu, Ratna R., Thomas, Stefani, Wang, Yue, White, Forest M., Whiteaker, Jeffrey R., Whiteley, Gordon A., Zhang, Hui, Zhang, Zhen, Zhao, Yingming, Zhu, Heng, Zimmerman, Lisa J., Krug, Karsten, Jaehnig, Eric J., Satpathy, Shankha, Blumenberg, Lili, Karpova, Alla, Anurag, Meenakshi, Miles, George, Mertins, Philipp, Geffen, Yifat, Tang, Lauren C., Heiman, David I., Cao, Song, Maruvka, Yosef E., Lei, Jonathan T., Huang, Chen, Kothadia, Ramani B., Colaprico, Antonio, Birger, Chet, Wang, Jarey, Dou, Yongchao, Wen, Bo, Shi, Zhiao, Liao, Yuxing, Wiznerowicz, Maciej, Wyczalkowski, Matthew A., Chen, Xi Steven, Kennedy, Jacob J., Paulovich, Amanda G., Thiagarajan, Mathangi, Kinsinger, Christopher R., Hiltke, Tara, Boja, Emily S., Mesri, Mehdi, Robles, Ana I., Rodriguez, Henry, Westbrook, Thomas F., Ding, Li, Getz, Gad, Clauser, Karl R., Fenyö, David, Ruggles, Kelly V., Zhang, Bing, Mani, D.R., Carr, Steven A., Ellis, Matthew J., Gillette, Michael A., Avanessian, Shayan C., Cai, Shuang, Chan, Daniel, Chen, Xian, Edwards, Nathan J., Hoofnagle, Andrew N., Kane, M. Harry, Ketchum, Karen A., Kuhn, Eric, Levine, Douglas A., Li, Shunqiang, Liebler, Daniel C., Liu, Tao, Luo, Jingqin, Madhavan, Subha, Maher, Chris, McDermott, Jason E., McGarvey, Peter B., Oberti, Mauricio, Pandey, Akhilesh, Payne, Samuel H., Ransohoff, David F., Rivers, Robert C., Rodland, Karin D., Rudnick, Paul, Sanders, Melinda E., Shaw, Kenna M., Shih, Ie-Ming, Slebos, Robbert J.C., Smith, Richard D., Snyder, Michael, Stein, Stephen E., Tabb, David L., Thangudu, Ratna R., Thomas, Stefani, Wang, Yue, White, Forest M., Whiteaker, Jeffrey R., Whiteley, Gordon A., Zhang, Hui, Zhang, Zhen, Zhao, Yingming, Zhu, Heng, and Zimmerman, Lisa J.

Abstract

© 2020 The Authors The integration of mass spectrometry-based proteomics with next-generation DNA and RNA sequencing profiles tumors more comprehensively. Here this “proteogenomics” approach was applied to 122 treatment-naive primary breast cancers accrued to preserve post-translational modifications, including protein phosphorylation and acetylation. Proteogenomics challenged standard breast cancer diagnoses, provided detailed analysis of the ERBB2 amplicon, defined tumor subsets that could benefit from immune checkpoint therapy, and allowed more accurate assessment of Rb status for prediction of CDK4/6 inhibitor responsiveness. Phosphoproteomics profiles uncovered novel associations between tumor suppressor loss and targetable kinases. Acetylproteome analysis highlighted acetylation on key nuclear proteins involved in the DNA damage response and revealed cross-talk between cytoplasmic and mitochondrial acetylation and metabolism. Our results underscore the potential of proteogenomics for clinical investigation of breast cancer through more accurate annotation of targetable pathways and biological features of this remarkably heterogeneous malignancy.

Published
2022

8. MONTE enables serial immunopeptidome, ubiquitylome, proteome, phosphoproteome, acetylome analyses of sample-limited tissues

Author

Abelin, Jennifer G., primary, Bergstrom, Erik J., additional, Taylor, Hannah B., additional, Rivera, Keith D., additional, Klaeger, Susan, additional, Xu, Charles, additional, White, C. Jackson, additional, Olive, Meagan E., additional, Maynard, Myranda, additional, Kane, M. Harry, additional, Rachimi, Suzanna, additional, Mani, D.R., additional, Gillette, Michael A., additional, Clauser, Karl R., additional, Udeshi, Namrata D., additional, and Carr, Steven A., additional

Published
2021
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9. Proteogenomic insights into the biology and treatment of HPV-negative head and neck squamous cell carcinoma

Author

Huang, Chen, primary, Chen, Lijun, additional, Savage, Sara R., additional, Eguez, Rodrigo Vargas, additional, Dou, Yongchao, additional, Li, Yize, additional, da Veiga Leprevost, Felipe, additional, Jaehnig, Eric J., additional, Lei, Jonathan T., additional, Wen, Bo, additional, Schnaubelt, Michael, additional, Krug, Karsten, additional, Song, Xiaoyu, additional, Cieślik, Marcin, additional, Chang, Hui-Yin, additional, Wyczalkowski, Matthew A., additional, Li, Kai, additional, Colaprico, Antonio, additional, Li, Qing Kay, additional, Clark, David J., additional, Hu, Yingwei, additional, Cao, Liwei, additional, Pan, Jianbo, additional, Wang, Yuefan, additional, Cho, Kyung-Cho, additional, Shi, Zhiao, additional, Liao, Yuxing, additional, Jiang, Wen, additional, Anurag, Meenakshi, additional, Ji, Jiayi, additional, Yoo, Seungyeul, additional, Zhou, Daniel Cui, additional, Liang, Wen-Wei, additional, Wendl, Michael, additional, Vats, Pankaj, additional, Carr, Steven A., additional, Mani, D.R., additional, Zhang, Zhen, additional, Qian, Jiang, additional, Chen, Xi S., additional, Pico, Alexander R., additional, Wang, Pei, additional, Chinnaiyan, Arul M., additional, Ketchum, Karen A., additional, Kinsinger, Christopher R., additional, Robles, Ana I., additional, An, Eunkyung, additional, Hiltke, Tara, additional, Mesri, Mehdi, additional, Thiagarajan, Mathangi, additional, Weaver, Alissa M., additional, Sikora, Andrew G., additional, Lubiński, Jan, additional, Wierzbicka, Małgorzata, additional, Wiznerowicz, Maciej, additional, Satpathy, Shankha, additional, Gillette, Michael A., additional, Miles, George, additional, Ellis, Matthew J., additional, Omenn, Gilbert S., additional, Rodriguez, Henry, additional, Boja, Emily S., additional, Dhanasekaran, Saravana M., additional, Ding, Li, additional, Nesvizhskii, Alexey I., additional, El-Naggar, Adel K., additional, Chan, Daniel W., additional, Zhang, Hui, additional, Zhang, Bing, additional, Agarwal, Anupriya, additional, Anderson, Matthew L., additional, Avanessian, Shayan C., additional, Avtonomov, Dmitry, additional, Bathe, Oliver F., additional, Birger, Chet, additional, Birrer, Michael J., additional, Blumenberg, Lili, additional, Bocik, William E., additional, Borate, Uma, additional, Borucki, Melissa, additional, Burke, Meghan C., additional, Cai, Shuang, additional, Calinawan, Anna Pamela, additional, Cerda, Sandra, additional, Charamut, Alyssa, additional, Chen, Lin S., additional, Chowdhury, Shrabanti, additional, Clauser, Karl R., additional, Culpepper, Houston, additional, Czernicki, Tomasz, additional, D'Angelo, Fulvio, additional, Day, Jacob, additional, De Young, Stephanie, additional, Demir, Emek, additional, Ding, Fei, additional, Domagalski, Marcin J., additional, Dort, Joseph C., additional, Druker, Brian, additional, Duffy, Elizabeth, additional, Dyer, Maureen, additional, Edwards, Nathan J., additional, Elburn, Kimberly, additional, Ermakova, Tatiana S., additional, Fenyo, David, additional, Ferrarotto, Renata, additional, Francis, Alicia, additional, Gabriel, Stacey, additional, Garofano, Luciano, additional, Geffen, Yifat, additional, Getz, Gad, additional, Goldthwaite, Charles A., additional, Hannick, Linda I., additional, Hariharan, Pushpa, additional, Hayes, David N., additional, Heiman, David, additional, Hindenach, Barbara, additional, Hoadley, Katherine A., additional, Hostetter, Galen, additional, Hyrcza, Martin, additional, Jewell, Scott D., additional, Jones, Corbin D., additional, Kane, M. Harry, additional, Karz, Alicia, additional, Kothadia, Ramani B., additional, Krek, Azra, additional, Kumar-Sinha, Chandan, additional, Liu, Tao, additional, Liu, Hongwei, additional, Ma, Weiping, additional, Malc, Ewa, additional, Malovannaya, Anna, additional, Mareedu, Sailaja, additional, Markey, Sanford P., additional, Marrero-Oliveras, Annette, additional, Maunganidze, Nicollette, additional, McDermott, Jason E., additional, McGarvey, Peter B., additional, McGee, John, additional, Mieczkowski, Piotr, additional, Migliozzi, Simona, additional, Montgomery, Rebecca, additional, Newton, Chelsea J., additional, Ozbek, Umut, additional, Paulovich, Amanda G., additional, Payne, Samuel H., additional, Pazardzhikliev, Dimitar Dimitrov, additional, Perou, Amy M., additional, Petralia, Francesca, additional, Petrenko, Lyudmila, additional, Piehowski, Paul D., additional, Placantonakis, Dmitris, additional, Polonskaya, Larisa, additional, Ponomareva, Elena V., additional, Potapova, Olga, additional, Qi, Liqun, additional, Qu, Ning, additional, Ramkissoon, Shakti, additional, Reva, Boris, additional, Richey, Shannon, additional, Robinson, Karna, additional, Roche, Nancy, additional, Rodland, Karin, additional, Rohrer, Daniel C., additional, Rykunov, Dmitry, additional, Schadt, Eric E., additional, Shi, Yan, additional, Shutack, Yvonne, additional, Singh, Shilpi, additional, Skelly, Tara, additional, Smith, Richard, additional, Sokoll, Lori J., additional, Stawicki, Jakub, additional, Stein, Stephen E., additional, Suh, James, additional, Szopa, Wojciech, additional, Tabor, Dave, additional, Tan, Donghui, additional, Tansil, Darlene, additional, Teo, Guo Ci, additional, Thangudu, Ratna R., additional, Tognon, Cristina, additional, Traer, Elie, additional, Tsang, Shirley, additional, Tyner, Jeffrey, additional, Um, Ki Sung, additional, Valley, Dana R., additional, Vasilev, Lyubomir Valkov, additional, Vatanian, Negin, additional, Velvulou, Uma, additional, Vernon, Michael, additional, Westbrook, Thomas F., additional, Whiteaker, Jeffrey R., additional, Wu, Yige, additional, Xu, Midie, additional, Yao, Lijun, additional, Yi, Xinpei, additional, Yu, Fengchao, additional, Zaalishvili, Kakhaber, additional, Zakhartsev, Yuriy, additional, Zelt, Robert, additional, Zhao, Grace, additional, and Zhu, Jun, additional

Published
2021
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10. Proteogenomic Landscape of Breast Cancer Tumorigenesis and Targeted Therapy

Author

Krug, Karsten, primary, Jaehnig, Eric J., additional, Satpathy, Shankha, additional, Blumenberg, Lili, additional, Karpova, Alla, additional, Anurag, Meenakshi, additional, Miles, George, additional, Mertins, Philipp, additional, Geffen, Yifat, additional, Tang, Lauren C., additional, Heiman, David I., additional, Cao, Song, additional, Maruvka, Yosef E., additional, Lei, Jonathan T., additional, Huang, Chen, additional, Kothadia, Ramani B., additional, Colaprico, Antonio, additional, Birger, Chet, additional, Wang, Jarey, additional, Dou, Yongchao, additional, Wen, Bo, additional, Shi, Zhiao, additional, Liao, Yuxing, additional, Wiznerowicz, Maciej, additional, Wyczalkowski, Matthew A., additional, Chen, Xi Steven, additional, Kennedy, Jacob J., additional, Paulovich, Amanda G., additional, Thiagarajan, Mathangi, additional, Kinsinger, Christopher R., additional, Hiltke, Tara, additional, Boja, Emily S., additional, Mesri, Mehdi, additional, Robles, Ana I., additional, Rodriguez, Henry, additional, Westbrook, Thomas F., additional, Ding, Li, additional, Getz, Gad, additional, Clauser, Karl R., additional, Fenyö, David, additional, Ruggles, Kelly V., additional, Zhang, Bing, additional, Mani, D.R., additional, Carr, Steven A., additional, Ellis, Matthew J., additional, Gillette, Michael A., additional, Avanessian, Shayan C., additional, Cai, Shuang, additional, Chan, Daniel, additional, Chen, Xian, additional, Edwards, Nathan J., additional, Hoofnagle, Andrew N., additional, Kane, M. Harry, additional, Ketchum, Karen A., additional, Kuhn, Eric, additional, Levine, Douglas A., additional, Li, Shunqiang, additional, Liebler, Daniel C., additional, Liu, Tao, additional, Luo, Jingqin, additional, Madhavan, Subha, additional, Maher, Chris, additional, McDermott, Jason E., additional, McGarvey, Peter B., additional, Oberti, Mauricio, additional, Pandey, Akhilesh, additional, Payne, Samuel H., additional, Ransohoff, David F., additional, Rivers, Robert C., additional, Rodland, Karin D., additional, Rudnick, Paul, additional, Sanders, Melinda E., additional, Shaw, Kenna M., additional, Shih, Ie-Ming, additional, Slebos, Robbert J.C., additional, Smith, Richard D., additional, Snyder, Michael, additional, Stein, Stephen E., additional, Tabb, David L., additional, Thangudu, Ratna R., additional, Thomas, Stefani, additional, Wang, Yue, additional, White, Forest M., additional, Whiteaker, Jeffrey R., additional, Whiteley, Gordon A., additional, Zhang, Hui, additional, Zhang, Zhen, additional, Zhao, Yingming, additional, Zhu, Heng, additional, and Zimmerman, Lisa J., additional

Published
2020
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11. Proteogenomic Characterization Reveals Therapeutic Vulnerabilities in Lung Adenocarcinoma

Author

Gillette, Michael A., primary, Satpathy, Shankha, additional, Cao, Song, additional, Dhanasekaran, Saravana M., additional, Vasaikar, Suhas V., additional, Krug, Karsten, additional, Petralia, Francesca, additional, Li, Yize, additional, Liang, Wen-Wei, additional, Reva, Boris, additional, Krek, Azra, additional, Ji, Jiayi, additional, Song, Xiaoyu, additional, Liu, Wenke, additional, Hong, Runyu, additional, Yao, Lijun, additional, Blumenberg, Lili, additional, Savage, Sara R., additional, Wendl, Michael C., additional, Wen, Bo, additional, Li, Kai, additional, Tang, Lauren C., additional, MacMullan, Melanie A., additional, Avanessian, Shayan C., additional, Kane, M. Harry, additional, Newton, Chelsea J., additional, Cornwell, MacIntosh, additional, Kothadia, Ramani B., additional, Ma, Weiping, additional, Yoo, Seungyeul, additional, Mannan, Rahul, additional, Vats, Pankaj, additional, Kumar-Sinha, Chandan, additional, Kawaler, Emily A., additional, Omelchenko, Tatiana, additional, Colaprico, Antonio, additional, Geffen, Yifat, additional, Maruvka, Yosef E., additional, da Veiga Leprevost, Felipe, additional, Wiznerowicz, Maciej, additional, Gümüş, Zeynep H., additional, Veluswamy, Rajwanth R., additional, Hostetter, Galen, additional, Heiman, David I., additional, Wyczalkowski, Matthew A., additional, Hiltke, Tara, additional, Mesri, Mehdi, additional, Kinsinger, Christopher R., additional, Boja, Emily S., additional, Omenn, Gilbert S., additional, Chinnaiyan, Arul M., additional, Rodriguez, Henry, additional, Li, Qing Kay, additional, Jewell, Scott D., additional, Thiagarajan, Mathangi, additional, Getz, Gad, additional, Zhang, Bing, additional, Fenyö, David, additional, Ruggles, Kelly V., additional, Cieslik, Marcin P., additional, Robles, Ana I., additional, Clauser, Karl R., additional, Govindan, Ramaswamy, additional, Wang, Pei, additional, Nesvizhskii, Alexey I., additional, Ding, Li, additional, Mani, D.R., additional, Carr, Steven A., additional, Webster, Alex, additional, Francis, Alicia, additional, Charamut, Alyssa, additional, Paulovich, Amanda G., additional, Perou, Amy M., additional, Godwin, Andrew K., additional, Karnuta, Andrii, additional, Marrero-Oliveras, Annette, additional, Hindenach, Barbara, additional, Pruetz, Barbara, additional, Kubisa, Bartosz, additional, Druker, Brian J., additional, Birger, Chet, additional, Jones, Corbin D., additional, Valley, Dana R., additional, Rohrer, Daniel C., additional, Zhou, Daniel Cui, additional, Chan, Daniel W., additional, Chesla, David, additional, Clark, David J., additional, Rykunov, Dmitry, additional, Tan, Donghui, additional, Ponomareva, Elena V., additional, Duffy, Elizabeth, additional, Burks, Eric J., additional, Schadt, Eric E., additional, Bergstrom, Erik J., additional, Fedorov, Eugene S., additional, Malc, Ewa, additional, Wilson, George D., additional, Chen, Hai-Quan, additional, Krzystek, Halina M., additional, Liu, Hongwei, additional, Culpepper, Houston, additional, Sun, Hua, additional, Zhang, Hui, additional, Day, Jacob, additional, Suh, James, additional, Whiteaker, Jeffrey R., additional, Eschbacher, Jennifer, additional, McGee, John, additional, Ketchum, Karen A., additional, Rodland, Karin D., additional, Robinson, Karna, additional, Hoadley, Katherine A., additional, Suzuki, Kei, additional, Um, Ki Sung, additional, Elburn, Kim, additional, Wang, Liang-Bo, additional, Chen, Lijun, additional, Hannick, Linda, additional, Qi, Liqun, additional, Sokoll, Lori J., additional, Wojtyś, Małgorzata, additional, Domagalski, Marcin J., additional, Gritsenko, Marina A., additional, Beasley, Mary B., additional, Monroe, Matthew E., additional, Ellis, Matthew J., additional, Dyer, Maureen, additional, Burke, Meghan C., additional, Borucki, Melissa, additional, Sun, Meng-Hong, additional, Roehrl, Michael H., additional, Birrer, Michael J., additional, Noble, Michael, additional, Schnaubelt, Michael, additional, Vernon, Michael, additional, Chaikin, Michelle, additional, Krotevich, Mikhail, additional, Khan, Munziba, additional, Selvan, Myvizhi Esai, additional, Roche, Nancy, additional, Edwards, Nathan J., additional, Vatanian, Negin, additional, Potapova, Olga, additional, Grady, Pamela, additional, McGarvey, Peter B., additional, Mieczkowski, Piotr, additional, Hariharan, Pushpa, additional, Madan, Rashna, additional, Thangudu, Ratna R., additional, Smith, Richard D., additional, Welsh, Robert J., additional, Zelt, Robert, additional, Mehra, Rohit, additional, Matteotti, Ronald, additional, Mareedu, Sailaja, additional, Payne, Samuel H., additional, Cottingham, Sandra, additional, Markey, Sanford P., additional, Chugh, Seema, additional, Smith, Shaleigh, additional, Tsang, Shirley, additional, Cai, Shuang, additional, Boca, Simina M., additional, Carter, Sonya, additional, Gabriel, Stacey, additional, De Young, Stephanie, additional, Stein, Stephen E., additional, Shankar, Sunita, additional, Krubit, Tanya, additional, Liu, Tao, additional, Skelly, Tara, additional, Bauer, Thomas, additional, Velvulou, Uma, additional, Ozbek, Umut, additional, Petyuk, Vladislav A., additional, Sovenko, Volodymyr, additional, Bocik, William E., additional, Maggio, William W., additional, Chen, Xi, additional, Shi, Yan, additional, Wu, Yige, additional, Hu, Yingwei, additional, Liao, Yuxing, additional, Zhang, Zhen, additional, and Shi, Zhiao, additional

Published
2020
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13. Circulating and intratumoral immune determinants of response to atezolizumab plus bevacizumab in patients with variant histology or sarcomatoid renal cell carcinoma.

Author

Saliby, Renee Maria, Zarif, Talal El, Bakouny, Ziad, Shah, Valisha, Xie, Wanling, Flippot, Ronan, Denize, Thomas, Kane, M Harry, Madsen, Katrine, Ficial, Miriam, Hirsch, Laure, Wei, Xiao, Steinharter, John, Harshman, Lauren, Vaishampayan, Ulka, Severgnini, Mariano, McDermott, David, Lee, Gwo-Shu Mary, Xu, Wenxin, and Allen, Eliezer Van

Subjects
THERAPEUTIC use of monoclonal antibodies, THERAPEUTIC use of antineoplastic agents, RENAL cell carcinoma, IMMUNE checkpoint inhibitors, ANTINEOPLASTIC agents, CONFERENCES & conventions, TUMOR markers, VASCULAR endothelial growth factors, SARCOMA
Abstract

Background Renal cell carcinoma of variant histology (vRCC) encompasses approximately 20% of RCC diagnoses. Due to a poor understanding of the different biologies of vRCCs, there is currently no standard of care for this type of tumor and guidelines are extrapolated from clear-cell RCC trials. A phase II trial of atezolizumab plus bevacizumab in patients with vRCC or sarcomatoid differentiation had an acceptable safety profile and evidence of clinical activity, particularly in tumors with positive PD-L1 expression or sarcomatoid differentiation. To better understand the determinants of immunotherapy response in this population, we characterized blood- and tissue-based immune markers for patients with vRCC, or any RCC histology with sarcomatoid differentiation, enrolled in this phase II trial of atezolizumab and bevacizumab. Methods We used patient data and biospecimens (blood and tumor) from a prospective phase-II clinical trial of the anti-PD-L1 antibody atezolizumab and the anti-VEGF-A antibody bevacizumab in patients with metastatic RCC with variant histology and/or sarcomatoid differentiation (NCT02724878). Blood samples were collected at baseline, prior to therapy (C1D1: cycle one day one), and on-treatment, following two cycles of therapy (C3D1: cycle three day one). Plasma was assayed for the levels of soluble factors (e.g., cytokines and growth factors), and peripheral blood mononuclear cells (PBMCs) were immunophenotyped using flow cytometry. In addition, formalin-fixed, paraffin-embedded (FFPE) archival or pre-treatment study tumor biopsies were analyzed by immunohistochemistry and immunofluorescence for enrolled subjects with available biospecimen. Baseline demographics, clinical characteristics, and treatment outcomes, including progression-free survival (PFS), overall survival (OS), and clinical benefit, were collected, and analyzed from the trial database. This study was approved by each participating institution's institutional review board, and all patients provided written informed consent. We used R (version 4.1.1) to carry out our analyses. We assessed the relationships between biomarker variables were analyzed using Pearson correlations and hierarchical clustering using Euclidean distance. All biomarker variables were Z-score normalized. We calculated an inflammatory module, the systemic inflammation score (SIS), which corresponds to the average score of the five highly correlated inflammatory cytokines: MIP-1b, IL-1, MCP-1, IL-6, and IL-13. We applied pair-wise Wilcoxon tests to evaluate the association of biomarkers with clinical benefit groups and log-rank-tests and univariate Cox regression models to evaluate the relationship of biomarkers with PFS and OS. Results With the exception of two angiogenic cytokines (VEGF-A and Angiopoietin 2) that were more abundant in patients with non-sarcomatoid tumors, baseline circulating cytokines (plasma) had similar distributions between sarcomatoid and non-sarcomatoid subgroups. Baseline circulating inflammatory cytokines were highly correlated with one another, forming an "inflammatory module" that was increased in IMDC-poor risk patients and was associated with worse PFS (p=0.028) and with resistance to therapy (p=0.033). At baseline, an elevated circulating VEGF-A level was associated with a lack of response (p=0.03) and worse PFS (p=0.021). However, a larger increase in on-treatment levels of circulating VEGF-A was associated with clinical benefit (p=0.01) and improved overall survival (p=0.0058). Among peripheral immune cell populations, an on-treatment decrease in circulating PD-L1+ T cells was associated with improved outcomes, with a reduction in CD4+ PD-L1+ (HR:0.62[0.49-0.91], p=0.016) and CD8+ PD-L1+ T cells (HR:0.59[0.39-0.87], p=0.009) correlated with improved PFS. Within the tumor itself, a higher percentage of terminally exhausted (PD-1+ and either TIM-3+ or LAG-3+) CD8+ T cells was associated with worse PFS (p=0.028). We observed similar trends for all of these results in different subgroups according to sarcomatoid status and histology. Conclusions Overall, these findings support the value of tumor and blood-based immune assessments in determining therapeutic benefit for patients with RCC receiving atezolizumab plus bevacizumab. Furthermore, they provide a foundation for future biomarker studies for patients with variant histology RCC receiving immunotherapy-based combinations. [ABSTRACT FROM AUTHOR]

Published
2023
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14. A proteogenomic portrait of lung squamous cell carcinoma.

Author

Satpathy, Shankha, Krug, Karsten, Jean Beltran, Pierre M., Savage, Sara R., Petralia, Francesca, Kumar-Sinha, Chandan, Dou, Yongchao, Reva, Boris, Kane, M. Harry, Avanessian, Shayan C., Vasaikar, Suhas V., Krek, Azra, Lei, Jonathan T., Jaehnig, Eric J., Omelchenko, Tatiana, Geffen, Yifat, Bergstrom, Erik J., Stathias, Vasileios, Christianson, Karen E., and Heiman, David I.

Subjects
*SQUAMOUS cell carcinoma, *DRUG target, *BIOMARKERS, *METABOLIC regulation, *SURVIVIN (Protein), *POST-translational modification, *LUNG cancer treatment
Abstract

Lung squamous cell carcinoma (LSCC) remains a leading cause of cancer death with few therapeutic options. We characterized the proteogenomic landscape of LSCC, providing a deeper exposition of LSCC biology with potential therapeutic implications. We identify NSD3 as an alternative driver in FGFR1-amplified tumors and low-p63 tumors overexpressing the therapeutic target survivin. SOX2 is considered undruggable, but our analyses provide rationale for exploring chromatin modifiers such as LSD1 and EZH2 to target SOX2-overexpressing tumors. Our data support complex regulation of metabolic pathways by crosstalk between post-translational modifications including ubiquitylation. Numerous immune-related proteogenomic observations suggest directions for further investigation. Proteogenomic dissection of CDKN2A mutations argue for more nuanced assessment of RB1 protein expression and phosphorylation before declaring CDK4/6 inhibition unsuccessful. Finally, triangulation between LSCC, LUAD, and HNSCC identified both unique and common therapeutic vulnerabilities. These observations and proteogenomics data resources may guide research into the biology and treatment of LSCC. [Display omitted] • Unsupervised clustering revealed subtype with EMT and phosphoprotein signatures • Potential therapeutic vulnerabilities included survivin, NSD3, LSD1, and EZH2 • Rb phosphorylation nominated as a biomarker for trials with CDK4/6 inhibitors • Detailed immune landscape analysis highlighted targetable points of immuneregulation Comprehensive proteogenomic characterization of lung squamous cell carcinomas and paired normal adjacent tissues identifies taxonomic subclasses, alternative driver events, and insights into immune modulation, as well as putative biomarkers and potential therapeutic targets. [ABSTRACT FROM AUTHOR]

Published
2021
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