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1. Autophagy promotes efficient T cell responses to restrict high-dose Mycobacterium tuberculosis infection in mice

Author

Feng, Siwei, McNehlan, Michael E., Kinsella, Rachel L., Sur Chowdhury, Chanchal, Chavez, Sthefany M., Naik, Sumanta K., McKee, Samuel R., Van Winkle, Jacob A., Dubey, Neha, Samuels, Amanda, Swain, Amanda, Cui, Xiaoyan, Hendrix, Skyler V., Woodson, Reilly, Kreamalmeyer, Darren, Smirnov, Asya, Artyomov, Maxim N., Virgin, Herbert W., Wang, Ya-Ting, and Stallings, Christina L.

Published
2024
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7. List of contributors

Author

Aizawa, Shin-Ichi, primary, Alberdi, Pilar, additional, Alexander, David C., additional, Alía, Alberto, additional, Allison, D.G., additional, Amyes, Sebastian G.B., additional, An, Haoran, additional, Andrade, María J., additional, Antelmann, Haike, additional, Arias, Cesar A., additional, Asensio, Miguel A., additional, Axell-House, Dierdre B., additional, Bae, Hee-Won, additional, Baena, Laura Muñoz, additional, Baig, Abdul Mannan, additional, Bailey, Spenser O., additional, Baize, Sylvain, additional, Baldi, Pablo C., additional, Barbosa, Angela Silva, additional, Barbuddhe, Sukhadeo B., additional, Bard, Emilie, additional, Barry, Eileen M., additional, Basarab, Gregory S., additional, Beloborodova, N.V, additional, Bermúdez, Elena, additional, Bidmos, Fadil A., additional, Bisgaard, Magne, additional, Blakely, Garry W., additional, Bloch, Evan, additional, Boesen, Thias Oberg, additional, Bose, Dipayan, additional, Botero, Javier Enrique, additional, Bouabe, Hicham, additional, Bouchard, Michael J., additional, Bozue, Joel A., additional, Bradbury, Richard S., additional, Brett Moreau, G., additional, Cabezas-Cruz, Alejandro, additional, Cai, Rong-Jun, additional, Calderón, Enrique J., additional, Cao, Boyang, additional, Carmena, David, additional, Carvalho, Eneas, additional, Caulfield, Amanda D., additional, Cen, Shan, additional, Chai, Jong-Yil, additional, Chamberland, Robin R., additional, Champredon, David, additional, Chan, Edward D., additional, Charbon, Godefroid, additional, Chato, Connor, additional, Chelomina, G.N., additional, Chen, Jingyu, additional, Chen, Min, additional, Chen, Shuyu, additional, Chen, Suilin, additional, Chen, Yanfei, additional, Chen, Zhaoyuan, additional, Cheng, Aimin, additional, Cheng, Keding, additional, Chiu, Charles Y., additional, Cho, You-Hee, additional, Christensen, Henrik, additional, Chrtdernevskaya, E.A., additional, Contreras, Adolfo, additional, Contreras, Marinela, additional, Córdoba, Juan J., additional, Córdoba, María G., additional, Costa, Rita, additional, Cote, Christopher K., additional, Cui, Xiangling, additional, Cui, Yujun, additional, Dacal, Elena, additional, Dammann, Allison N., additional, Das, Shubhagata, additional, Dashti, Alejandro, additional, de la Fuente, José, additional, de la Garza, Mireya, additional, Delgado, Josué, additional, Delgado-Cuesta, Juan, additional, Deng, Haiteng, additional, Deng, Li, additional, Dey, Debajit, additional, Dhama, Kuldeep, additional, Diego, Juan García-Bernalt, additional, Ding, Hao, additional, Doern, Christopher D., additional, Dorman, Charles J., additional, Du, Zongmin, additional, Dunbar, Sherry A., additional, Duthie, Malcolm, additional, Dybvig, Kevin F., additional, Eakin, Ann E., additional, Eallonardo, Samuel J., additional, Eberly, Allison R., additional, Echeverry, Adriana Jaramillo, additional, Egland, Paul G., additional, El Zowalaty, Mohamed E., additional, Endsley, Janice Jones, additional, Eom, Keeseon S., additional, Evans, Benjamin A., additional, Falkinham, Joseph O., additional, Feng, Siwei, additional, Feng, Yaoyu, additional, Feng, Zongdi, additional, Fernández-Soto, Pedro, additional, Ferreira, Roux-Cil, additional, Flores-Huerta, Nadia, additional, Foster, Timothy J., additional, Fox-Moon, Sandra M., additional, Fraga, Tatiana Rodrigues, additional, Fredricks, David N., additional, Freitag, Nancy E., additional, Frimodt-Møller, Jakob, additional, Fuller, Risa, additional, Ganesh, Balasubramanian, additional, Gao, Ning, additional, García-Carnero, Laura C., additional, Garzetti, Debora, additional, Geoghegan, Joan A., additional, Ghenim, Raed, additional, Giambartolomei, Guillermo H., additional, Gilbert, Nicole M., additional, Gillis, Thomas Phillip, additional, Gladstone, Camilla A., additional, Gómez-Gaviria, Manuela, additional, Gómez-Marín, Jorge E., additional, Gong, Tengfang, additional, González, Ramón A., additional, Gray-Owen, Scott D., additional, Gu, Bing, additional, Guzmán-Téllez, Paula, additional, Hajal, Caroline, additional, Han, Yanping, additional, Hao, Yi, additional, Harrington, Amanda T., additional, Harris, Jason B., additional, Harvill, Eric T., additional, Hasan, S. Saif, additional, He, Guang-Jun, additional, He, Yongqun, additional, Heffron, Jared D., additional, Hidalgo, Paloma, additional, Hindiyeh, Musa Y., additional, Hreha, Teri N., additional, Hu, Xiaoyu, additional, Huang, Guanghua, additional, Huang, Jiangqing, additional, Huang, Liang, additional, Huang, Shifeng, additional, Huang, Xingxu, additional, Huang, Xueting, additional, Huang, Yilun, additional, Huffman, Anthony, additional, Humphreys, Tricia L., additional, Hunstad, David A., additional, Inglis, Timothy J.J., additional, Isaac, Lourdes, additional, Jacobs, Samantha E., additional, Janowicz, Diane M., additional, Jeon, Hyeong-Kyu, additional, Ji, Quanjiang, additional, Jia, Qi, additional, Jia, Wei, additional, Jin, Shouguang, additional, Jneidi, Lama, additional, Jose, Shinsmon, additional, Jung, Bong-Kwang, additional, Kattan, Randa, additional, Kaushik, Rahul, additional, Khare, Reeti, additional, Kim, Eun Sook, additional, Kirn, Thomas J., additional, Koo, Hyun, additional, Köster, Pamela C., additional, Krause, Peter J., additional, Kumar, Sanjai, additional, Kupz, Andreas, additional, Lambert, P.A., additional, Lamont, Richard J., additional, Langford, Paul R., additional, Lebeaux, David, additional, Legname, Giuseppe, additional, Li, Bin, additional, Li, Chunhao, additional, Li, Fen, additional, Li, Jun, additional, Li, Lanjuan, additional, Li, Ruofan, additional, Li, Ruoyu, additional, Li, Ting, additional, Li, Yang-Yang, additional, Li, Yanhua, additional, Li, Zhuorong, additional, Liang, Xiaomeng, additional, Liao, Guojian, additional, Lin, Ping, additional, Ling, Yun, additional, Liu, Bo, additional, Liu, Dongyou, additional, Liu, Guohua, additional, Liu, Huidi, additional, Liu, Jiafeng, additional, Liu, Jintao, additional, Liu, Qi, additional, Liu, Shu-Lin, additional, Liu, Taiping, additional, Liu, Tongbao, additional, Liu, Wei, additional, Liu, Yan, additional, Liu, Yanni, additional, Liu, Yisong, additional, Liu, Yuan, additional, Løbner-Olesen, Anders, additional, Loeffelholz, Michael, additional, Lu, Hongzhou, additional, Luna, Brian, additional, Ma, Bingting, additional, Ma, Chengying, additional, Ma, Shuang, additional, Ma, TianLi, additional, Madan, Rajat, additional, Mahle, Rachael E., additional, Mahlen, Steven D., additional, Malik, Satya Veer Singh, additional, Malik, Yashpal Singh, additional, Malvy, Denis, additional, Mann, Barbara J., additional, Marasini, Daya, additional, Maris, Alexander S., additional, Marjomäki, Varpu, additional, Marjuki, Henju, additional, Martín, Alberto, additional, Martín, Irene, additional, Martínez-Castillo, Moisés, additional, Martínez-Pabón, María Cecilia, additional, Mathison, Blaine A., additional, Ma’ayeh, Showgy, additional, McDowell, Andrew, additional, McLaughlin, Stephanie E., additional, McSheffrey, Gordon G., additional, Medrano, Francisco J., additional, Meehan, Conor J., additional, Mehta, Dhwani, additional, Mejía-Oquendo, Manuela, additional, Melo-Cristino, José, additional, Mendoza-Barberá, Elena, additional, Meng, Xinan, additional, Merino, Susana, additional, Merritt, Adam J., additional, Miller, Steve, additional, Miller, William R., additional, Minamino, Tohru, additional, Mirzaei, Mohammadali Khan, additional, Mora-Montes, Héctor M., additional, Mortensen, Joel, additional, Mostafa, Heba H., additional, Muhsen, Khitam, additional, Mujahed, Ahlam, additional, Muro, Antonio, additional, Murphy, Olwen C., additional, Newton, Hayley J., additional, Nguyen, April H., additional, Nichols, Wright W., additional, Niu, Siqiang, additional, Núñez, Félix, additional, Obregon, Dasiel, additional, Okamoto, Akira, additional, Okutani, Akiko, additional, Olabode, Abayomi, additional, Omar, Muna, additional, Ong, Edison, additional, Ouyang, Zhiming, additional, Pacak, Christina A., additional, Pacheco-Yépez, Judith, additional, Palmer, John, additional, Pang, Xiaoli, additional, Paredes-Sabja, Daniel, additional, Peng, Zhong, additional, Peng, Zonggen, additional, Pérez-Nevado, Francisco, additional, Poon, Art, additional, Pospíšilová, Petra, additional, Potts, Caelin C., additional, Pu, Qinqin, additional, Pujic, Petar, additional, Qi, Rui, additional, Qian, Chenyun, additional, Qian, Liu, additional, Qin, Aiping, additional, Qu, Fen, additional, Rakin, Alexander, additional, Ramesh, Ashwin, additional, Ramirez, Mario, additional, Rao, Yu, additional, Ratner, Adam J., additional, Rawool, Deepak B., additional, Rehman, Asma, additional, Ren, Jie, additional, Ren, Ping, additional, Retchless, Adam C., additional, Robertson, Erle S., additional, Rodríguez, Alicia, additional, Rodriguez, Azucena, additional, Rodríguez-Medina, Carolina, additional, Rodriguez-Nava, Veronica, additional, Rohde, Manfred, additional, Romero-Rodríguez, Alba, additional, Rosales-Morgan, Gabriela, additional, Rosenkranz, Andrea L., additional, Ruiz-Moyano, Santiago, additional, Ruokolainen, Visa, additional, Sabateen, Ali, additional, Sahu, Radhakrishna, additional, Sails, Andrew, additional, Sang, Yu, additional, Santana, Clarissa H., additional, Santos, Jesus A., additional, Santos, Renato L., additional, Schmitz, Jonathan E., additional, Serrano-Luna, Jesús, additional, Shen, Jianzhong, additional, Shen, Zhangqi, additional, Shibayama, Mineko, additional, Shirtliff, Mark E., additional, Silva-Costa, Catarina, additional, Silva-Olivares, Angélica, additional, Singh, Niraj Kumar, additional, Šmajs, David, additional, Smith, Robert P., additional, Smith, Sophie, additional, Snyder, Lori A.S., additional, Song, Yinggai, additional, Soro, Aurea Simon, additional, Spearman, Paul, additional, Spellberg, Brad, additional, Sprague, Lisa D., additional, Stratton, Charles W., additional, Strenk, Susan M., additional, Strugnell, Richard A., additional, Sun, Keer, additional, Suo, Xun, additional, Suzuki-Hatano, Silveli, additional, Svärd, Staffan, additional, Talbot, Elizabeth A., additional, Tamez-Castrellón, Alma K., additional, Tan, Nie, additional, Tang, Cynthia Y., additional, Tang, Yi-Wei, additional, Tao, Jia, additional, Tao, Lili, additional, Terrero-Salcedo, David, additional, Tharmalingam, Jayaraman, additional, Thwe, Phyu M., additional, Tiamani, Kawtar, additional, Tomás, Juan M., additional, Topaz, Nadav, additional, Tsai, Ang-Chen, additional, Tsalik, Ephraim L., additional, Tuomanen, Elaine I., additional, Turenne, Christine Y., additional, Tyagi, Anuj, additional, Uprety, Priyanka, additional, Valour, Florent, additional, van Hensbergen, Vincent P., additional, Venkatesan, Arun, additional, Vergis, Jess, additional, Villar, Margarita, additional, Vollmer, Waldemar, additional, Waites, Ken B., additional, Wan, Xiu-Feng, additional, Wang, Guiqing, additional, Wang, Lijun, additional, Wang, Lin, additional, Wang, Linqi, additional, Wang, Xiangru, additional, Wang, Xin, additional, Wang, Xinjie, additional, Wang, Ya-Ting, additional, Wang, Yang, additional, Wang, Yating, additional, Weil, Ana A., additional, Welkos, Susan L., additional, Wengenack, Nancy L., additional, Westblade, Lars F., additional, Whitfield, Chris, additional, Wu, Hui, additional, Wu, Lijuan, additional, Wu, Min, additional, Wu, Yarong, additional, Wu, Zhaowei, additional, Xiang, Ye, additional, Xiao, Di, additional, Xiao, Li, additional, Xiao, Lihua, additional, Xu, Tao, additional, Xu, Wenyue, additional, Xu, Xinping, additional, Xue, Jinling, additional, Yadav, Jay Prakash, additional, Yan, Junxiang, additional, Yan, Yixin, additional, Yang, Changmei, additional, Yang, Ruifu, additional, Yang, Ying, additional, Yao, Kaihu, additional, Yao, Yu-Feng, additional, Yeakle, Kyle C., additional, Yu, Demin, additional, Yu, Hao, additional, Yu, Xue-Jie, additional, Yuan, Zhenghong, additional, Zai, Wenjing, additional, Zhang, Jianzhong, additional, Zhang, Jing-Ren, additional, Zhang, Lanyue, additional, Zhang, Lijie, additional, Zhang, Qiwei, additional, Zhang, Wenbao, additional, Zhang, Wenhong, additional, Zhang, Xinxin, additional, Zhao, Youbao, additional, Zhou, Chuanmin, additional, Zhu, Feng, additional, Zhu, Jingting, additional, and Zhu, Yongqun, additional

Published
2024
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10. Global existence and large time behavior of weak solutions to the two-phase flow

Author

Wang, Ya-Ting and Shou, Ling-Yun

Subjects
Mathematics - Analysis of PDEs
Abstract

In this paper, we consider a two-phase flow model consisting of the compressible Navier-Stokes systems with degenerate viscosity coupled with the compressible Navier-Stokes systems with constant viscosities via a drag force, which can be derived from Chapman-Enskog expansion for the compressible Navier-Stokes-Vlasov-Fokker-Planck system. For general initial data, we establish the global existence of weak solutions with finite energy to the initial value problem in the three-dimensional periodic domain, and prove the convergence of global weak solutions to its equilibrium state as the time tends to infinity., Comment: 38 pages

Published
2022

17. Thermodynamic properties of ideal Bose gas trapped in different external power-law potentials under generalized uncertainty principle*

Author

Wang, Ya-ting and Li, He-ling

Subjects
Condensed Matter - Quantum Gases
Abstract

Significant evidence is available to support the quantum effects of gravity that leads to the generalized uncertainty principle (GUP) and the minimum observable length. Usually quantum mechanics, statistical physics doesn't take gravity into account. Thermodynamic properties of ideal Bose gases in different external power-law potentials are studied under GUP with statistical physical method. Critical temperature, internal energy, heat capacity, entropy, particles number of ground state and excited state are calculated analytically to ideal Bose gases in the external potentials under GUP. Below the critical temperature, taking rubidium and sodium atoms ideal Bose gases whose particle densities are under standard and experimental conditions, respectively, as examples, the relations of internal energy, heat capacity and entropy with temperature are analyzed numerically. Theoretical and numerical calculations show that: GUP leads to an increase in the critical temperature. When the temperature is lower than the critical temperature and slightly higher than zero Kelvin, GUP's amendments to internal energy, heat capacity and entropy are positive; As the temperature increases to a certain value, these amendments become negative. The external potentials can increase or decrease the influence of GUP on thermodynamic properties. Under the initial experimental conditions when Bose-Einstein condensation was first verified by sodium atomic gas, the influence of GUP can be completely ignored. Under certain conditions, GUP may become the dominant factor governing the thermodynamic properties of the system.

Published
2020
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33. The representation of sustainable development goals in a national curriculum: a content analysis of Taiwan's 12-Year Basic Education Curriculum Guidelines.

Author

Chou, Pei-I and Wang, Ya-Ting

Subjects
*CONTENT analysis, *BASIC education, *COURSE content (Education), *ENVIRONMENTAL education
Abstract

Despite the increasing focus on incorporating the Sustainable Development Goals (SDGs) into education through curriculum mainstreaming, related research remains lacking. This study explored the representation of SDGs in Taiwan's national curriculum in terms of selection and organization. Through a content analysis of the social studies and natural sciences curriculum guidelines, the findings revealed that SDG-related content comprises a minor part of the guidelines and is not well organized, possibly due to limitations on discipline characteristics and curriculum types. A subtle but complex implicit curriculum reflects neoliberalism, which addresses SDG-related issues through market mechanisms and shifts the focus from power, politics, and citizenship to consumers' choices and lifestyles. The results provide a reference for policymakers and educators in re-examining underrepresented SDGs and dimensions and organizing them coherently. They also bridge the gap between the international framework and national curricula, laying the foundation for international comparisons, discussions, and debates on ESD. [ABSTRACT FROM AUTHOR]

Published
2024
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34. Intestinal tuft cell immune privilege enables norovirus persistence.

Author

Strine, Madison S., Fagerberg, Eric, Darcy, Patrick W., Barrón, Gabriel M., Filler, Renata B., Alfajaro, Mia Madel, D'Angelo-Gavrish, Nicole, Wang, Fang, Graziano, Vincent R., Menasché, Bridget L., Damo, Martina, Wang, Ya-Ting, Howitt, Michael R., Lee, Sanghyun, Joshi, Nikhil S., Mucida, Daniel, and Wilen, Craig B.

Subjects
NOROVIRUSES, T cell receptors, T cells, INTESTINES, NOROVIRUS diseases, SURGICAL site infections
Abstract

The persistent murine norovirus strain MNVCR6 is a model for human norovirus and enteric viral persistence. MNVCR6 causes chronic infection by directly infecting intestinal tuft cells, rare chemosensory epithelial cells. Although MNVCR6 induces functional MNV-specific CD8+ T cells, these lymphocytes fail to clear infection. To examine how tuft cells promote immune escape, we interrogated tuft cell interactions with CD8+ T cells by adoptively transferring JEDI (just EGFP death inducing) CD8+ T cells into Gfi1b-GFP tuft cell reporter mice. Unexpectedly, some intestinal tuft cells partially resisted JEDI CD8+ T cell–mediated killing—unlike Lgr5+ intestinal stem cells and extraintestinal tuft cells—despite seemingly normal antigen presentation. When targeting intestinal tuft cells, JEDI CD8+ T cells predominantly adopted a T resident memory phenotype with decreased effector and cytotoxic capacity, enabling tuft cell survival. JEDI CD8+ T cells neither cleared nor prevented MNVCR6 infection in the colon, the site of viral persistence, despite targeting a virus-independent antigen. Ultimately, we show that intestinal tuft cells are relatively resistant to CD8+ T cells independent of norovirus infection, representing an immune-privileged niche that can be leveraged by enteric microbes. Editor's summary: Norovirus is a major cause of acute foodborne illness that can also lead to persistent infections. Specialized chemosensory epithelial cells called tuft cells are the target cell for murine norovirus, but how chronic infections are established remains unclear. Using mice with CD8+ T cells bearing a fluorescent protein-specific T cell receptor, Strine et al. found that intestinal tuft cells are intrinsically resistant to CD8+ T cell–mediated killing compared with other gut epithelial cells. Tuft cell–mediated immune evasion from CD8+ T cells enabled norovirus persistence in the colon. These findings indicate that intestinal tuft cells represent an immune-privileged niche that is intrinsically resistant to T cell responses. —Claire Olingy [ABSTRACT FROM AUTHOR]

Published
2024
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36. Select autophagy genes maintain quiescence of tissue-resident macrophages and increase susceptibility to Listeria monocytogenes

Author

Wang, Ya-Ting, Zaitsev, Konstantin, Lu, Qun, Li, Shan, Schaiff, W. Timothy, Kim, Ki-Wook, Droit, Lindsay, Wilen, Craig B., Desai, Chandni, Balce, Dale R., Orchard, Robert C., Orvedahl, Anthony, Park, Sunmin, Kreamalmeyer, Darren, Handley, Scott A., Pfeifer, John D., Baldridge, Megan T., Artyomov, Maxim N., Stallings, Christina L., and Virgin, Herbert W.

Published
2020
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38. Tropism for tuft cells determines immune promotion of norovirus pathogenesis

Author

Wilen, Craig B., Lee, Sanghyun, Hsieh, Leon L., Orchard, Robert C., Desai, Chandni, Hykes, Barry L., McAllaster, Michael R., Balce, Dale R., Feehley, Taylor, Brestoff, Jonathan R., Hickey, Christina A., Yokoyama, Christine C., Wang, Ya-Ting, MacDuff, Donna A., Kreamalmayer, Darren, Howitt, Michael R., Neil, Jessica A., Cadwell, Ken, Allen, Paul M., Handley, Scott A., van Lookeren Campagne, Menno, Baldridge, Megan T., and Virgin, Herbert W.

Published
2018

45. Author Correction: Select autophagy genes maintain quiescence of tissue-resident macrophages and increase susceptibility to Listeria monocytogenes

Author

Wang, Ya-Ting, Zaitsev, Konstantin, Lu, Qun, Li, Shan, Schaiff, W. Timothy, Kim, Ki-Wook, Droit, Lindsay, Wilen, Craig B., Desai, Chandni, Balce, Dale R., Orchard, Robert C., Orvedahl, Anthony, Park, Sunmin, Kreamalmeyer, Darren, Handley, Scott A., Pfeifer, John D., Baldridge, Megan T., Artyomov, Maxim N., Stallings, Christina L., and Virgin, Herbert W.

Published
2021
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46. Establishing the Core Concepts and Competence Indicators of Global/International Education for Taiwan's Grade 1-9 Curriculum Guidelines

Author

Chou, Pei-I, Cheng, Ming-Chang, Lin, Yen-Ling, and Wang, Ya-Ting

Abstract

The development of standards, or indicators, for global/international education has lagged behind that of the national curriculum. To address this, we developed a set of core concepts and competence indicators of global/international education for Taiwan's "Grade 1-9 Curriculum Guidelines" and revised these through three rounds of Delphi surveys. The final version is composed of five core concepts, three dimensions, and 60 competence indicators across seven learning areas accessed through four learning stages. To explore the extent to which the national curriculum overlaps with global/international education, we conducted content analysis to examine the global/international components of the guidelines. This revealed that 10.70% of the competence indicators in the guidelines were related to global core concepts. Numerous indicators were related to multiculture, whereas only a few were related to human rights and social justice. The comparison of the indicators for learning areas showed that integrative activities indicators were the most closely related to global education, whereas social studies indicators were related to all global core concepts. The mathematics indicators were unintegrated with global core concepts, with most of the learning areas emphasizing only one or two such concepts.

Published
2015
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47. Ubiquitination of tumor suppressor PML regulates prometastatic and immunosuppressive tumor microenvironment

Author

Wang, Ya-Ting, Chen, Jocelyn, Chang, Chou-Wei, Jen, Jayu, Huang, Tzu-Yu, Chen, Chun-Ming, Shen, Roger, Liang, Suh-Yuen, Cheng, I-Cheng, Yang, Shuenn-Chen, Lai, Wu-Wei, Cheng, Kuang-Hung, Hsieh, Tao-Shih, Lai, Ming-Zong, Cheng, Hung-Chi, Wang, Yi-Ching, and Chen, Ruey-Hwa

Subjects
Lung cancer -- Care and treatment -- Diagnosis -- Development and progression, Ubiquitin-proteasome system -- Analysis, Leukemia -- Analysis -- Prognosis -- Development and progression -- Care and treatment -- Diagnosis, Cancer metastasis -- Diagnosis -- Development and progression, Health care industry
Abstract

The tumor microenvironment plays an important role in tumor growth and metastasis. However, the mechanism by which tumor cells regulate the cell and non-cell constituents of surrounding stroma remains incompletely understood. Promyelocytic leukemia (PML) is a pleiotropic tumor suppressor, but its role in tumor microenvironment regulation is poorly characterized. PML is frequently downregulated in many cancer types, including lung cancer. Here, we identify a PML ubiquitination pathway that is mediated by WD repeat 4-containing cullin-RING ubiquitin ligase 4 ([CRL4.sup.WDR4]). Clinically, this PML degradation pathway is hyperactivated in lung cancer and correlates with poor prognosis. The WDR4/PML axis induces a set of cell-surface or secreted factors, including CD73, urokinase-type plasminogen activator receptor (uPAR), and serum amyloid A2 (SAA2), which elicit paracrine effects to stimulate migration, invasion, and metastasis in multiple lung cancer models. In xenograft and genetically engineered mouse models, the WDR4/PML axis elevates intratumoral Tregs and M2-like macrophages and reduces [CD8.sup.+] T cells to promote lung tumor growth. These immunosuppressive effects were all reversed by CD73 blockade. Our study identifies WDR4 as an oncoprotein that negatively regulates PML via ubiquitination to promote lung cancer progression by fostering an immunosuppressive and prometastatic tumor microenvironment, suggesting the potential of immune-modulatory approaches for treating lung cancer with aberrant PML degradation., Introduction Lung cancer is one of the most devastating diseases. Despite advances in treatment, the 5-year survival rate is only slightly better than 10%, and the majority of late-stage patients [...]

Published
2017
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