Obstacles Posed by the Tumor Microenvironment to T cell Activity: A Case for Synergistic Therapies
TLDR
How the tumor and its microenvironment influences T cell trafficking and function with a focus on melanoma, and pancreatic and ovarian cancer, is discussed, and how scientific advances may help overcome these hurdles are discussed.About:
This article is published in Cancer Cell.The article was published on 2017-03-13 and is currently open access. It has received 453 citations till now. The article focuses on the topics: Tumor microenvironment & Tumor progression.read more
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Cancer immunoediting and resistance to T cell-based immunotherapy
Jake S. O’Donnell,Jake S. O’Donnell,Michele W.L. Teng,Michele W.L. Teng,Mark J. Smyth,Mark J. Smyth +5 more
TL;DR: How a deeper understanding of the mechanisms underlying the cancer immunoediting process can provide insight into the development of resistance to immunotherapies and the strategies that can be used to overcome such resistance is discussed.
Journal ArticleDOI
Macrophages impede CD8 T cells from reaching tumor cells and limit the efficacy of anti–PD-1 treatment
Elisa Peranzoni,Elisa Peranzoni,Jean Lemoine,Jean Lemoine,Lene Vimeux,Lene Vimeux,Vincent Feuillet,Vincent Feuillet,Sarah Barrin,Sarah Barrin,Chahrazade Kantari-Mimoun,Chahrazade Kantari-Mimoun,Nadège Bercovici,Nadège Bercovici,Marion V. Guérin,Marion V. Guérin,Jérôme Biton,Hanane Ouakrim,Fabienne Régnier,Fabienne Régnier,Audrey Lupo,Marco Alifano,Diane Damotte,Emmanuel Donnadieu,Emmanuel Donnadieu +24 more
TL;DR: Evidence is provided that tumor-associated macrophages (TAMs) are an important determinant of the establishment of a T cell-excluded tumor phenotype, and the reduction of macrophage-mediated T cell exclusion increases tumor surveillance by CD8 T cells and renders tumors more responsive to anti-PD-1 treatment.
Journal ArticleDOI
Senolytic CAR T cells reverse senescence-associated pathologies.
Corina Amor,Judith Feucht,Josef Leibold,Yu-Jui Ho,Changyu Zhu,Direna Alonso-Curbelo,Jorge Mansilla-Soto,Jacob A. Boyer,Xiang Li,Xiang Li,Theodoros Giavridis,Amanda Kulick,Shauna L. Houlihan,Ellinor I.B. Peerschke,Scott L. Friedman,Vladimir Ponomarev,Alessandra Piersigilli,Michel Sadelain,Scott W. Lowe,Scott W. Lowe +19 more
TL;DR: Chimeric antigen receptor (CAR) T cells targeting uPAR, a cell-surface protein that is upregulated on senescent cells, eliminate senescence cells in vitro and in vivo and reduce liver fibrosis in mice.
Journal ArticleDOI
Integrated Proteogenomic Characterization of Clear Cell Renal Cell Carcinoma.
David J. Clark,Saravana M. Dhanasekaran,Francesca Petralia,Jianbo Pan,Xiaoyu Song,Yingwei Hu,Felipe da Veiga Leprevost,Boris Reva,Tung-Shing M. Lih,Hui Yin Chang,Weiping Ma,Chen Huang,Christopher J. Ricketts,Lijun Chen,Azra Krek,Yize Li,Dmitry Rykunov,Qing Kay Li,Lin Chen,Umut Ozbek,Suhas Vasaikar,Yige Wu,Seungyeul Yoo,Shrabanti Chowdhury,Matthew A. Wyczalkowski,Jiayi Ji,Michael Schnaubelt,Andy T. Kong,Sunantha Sethuraman,Dmitry M. Avtonomov,Minghui Ao,Antonio Colaprico,Song Cao,Kyung-Cho Cho,Selim Kalayci,Shiyong Ma,Wenke Liu,Kelly V. Ruggles,Anna Calinawan,Zeynep H. Gümüş,Daniel J. Geiszler,Emily Kawaler,Guo Ci Teo,Bo Wen,Yuping Zhang,Sarah Keegan,Kai Li,Feng Chen,Nathan Edwards,Phillip M. Pierorazio,Xi Steven Chen,Christian P. Pavlovich,A. Ari Hakimi,Gabriel Bromiński,James J. Hsieh,Andrzej Antczak,Tatiana Omelchenko,Jan Lubinski,Maciej Wiznerowicz,Maciej Wiznerowicz,W. Marston Linehan,Christopher R. Kinsinger,Mathangi Thiagarajan,Emily S. Boja,Mehdi Mesri,Tara Hiltke,Ana I. Robles,Henry Rodriguez,Jiang Qian,David Fenyö,Bing Zhang,Li Ding,Eric E. Schadt,Arul M. Chinnaiyan,Zhen Zhang,Gilbert S. Omenn,Marcin Cieslik,Daniel W. Chan,Alexey I. Nesvizhskii,Pei Wang,Hui Zhang,Abdul Samad Hashimi,Alexander R. Pico,Alla Y. Karpova,Alyssa Charamut,Amanda G. Paulovich,Amy M. Perou,Anna Malovannaya,Annette Marrero-Oliveras,Anupriya Agarwal,Barbara Hindenach,Barbara Pruetz,Beom-Jun Kim,Brian J. Druker,Chelsea J. Newton,Chet Birger,Corbin D. Jones,Cristina E. Tognon,D. R. Mani,Dana R. Valley,Daniel C. Rohrer,Daniel C. Zhou,Darlene Tansil,David Chesla,David I. Heiman,David C. Wheeler,Donghui Tan,Doug W. Chan,Emek Demir,Ewa P. Malc,Francesmary Modugno,Gaddy Getz,Galen Hostetter,George D. Wilson,Gerald W. Hart,Heng Zhu,Hongwei Liu,Houston Culpepper,Hua Sun,Hua Zhou,Jacob J. Day,James Suh,Jasmine Huang,Jason E. McDermott,Jeffrey R. Whiteaker,Jeffrey W. Tyner,Jennifer M. Eschbacher,Jin Chen,John McGee,Jun Zhu,Karen A. Ketchum,Karin D. Rodland,Karl R. Clauser,Karna Robinson,Karsten Krug,Katherine A. Hoadley,Ki Sung Um,Kim Elburn,Kimberly R. Holloway,Liang-Bo Wang,Lili Blumenberg,Linda Hannick,Liqun Qi,Lori J. Sokoll,MacIntosh Cornwell,Marc M. Loriaux,Marcin J. Domagalski,Marina A. Gritsenko,Matthew L. Anderson,Matthew E. Monroe,Matthew J. Ellis,Maureen Dyer,Meenakshi Anurag,Meghan C. Burke,Melissa Borucki,Michael A. Gillette,Michael J. Birrer,Michael T. Lewis,Michael Ittmann,Michael Smith,Michael Vernon,Michelle Chaikin,Milan G. Chheda,Munziba Khan,Nancy Roche,Nathan Edwards,Negin Vatanian,Nicole Tignor,Noam D. Beckmann,Pamela Grady,Patricia Castro,Paul D. Piehowski,Peter B. McGarvey,Piotr A. Mieczkowski,Pushpa Hariharan,Qingsong Gao,Rajiv Dhir,Ramani B. Kothadia,Ratna R. Thangudu,Rebecca I. Montgomery,Reyka G Jayasinghe,Richard D. Smith,Robert Edwards,Robert Zelt,Ross Bremner,Ruiyang Liu,Runyu Hong,Sailaja Mareedu,Samuel H. Payne,Sandra Cottingham,Sanford P. Markey,Scott D. Jewell,Shalin Patel,Shankha Satpathy,Shannon Richey,Sherri R. Davies,Shuang Cai,Simina M. Boca,Snehal Patil,Sohini Sengupta,Sonya Carter,Stacey Gabriel,Stefani N. Thomas,Stephanie De Young,Stephen E. Stein,Steven A. Carr,Steven M. Foltz,Sue Hilsenbeck,Tanya Krubit,Tao Liu,Tara Skelly,Thomas F. Westbrook,Uma Borate,Uma Velvulou,Vladislav A. Petyuk,William Bocik,Xi Chen,Yan Shi,Yifat Geffen,Yihao Lu,Ying Wang,Yosef E. Maruvka,Zhi Li,Zhiao Shi,Zhidong Tu +224 more
TL;DR: A large-scale proteogenomic analysis of ccRCC is reported to discern the functional impact of genomic alterations and provides evidence for rational treatment selection stemming fromccRCC pathobiology.
Journal ArticleDOI
Ex Vivo Profiling of PD-1 Blockade Using Organotypic Tumor Spheroids
Russell W. Jenkins,Amir Reza Aref,Patrick H. Lizotte,Elena Ivanova,Susanna Stinson,Chensheng W. Zhou,Michaela Bowden,Jiehui Deng,Hongye Liu,Diana Miao,Diana Miao,Meng Xiao He,Meng Xiao He,William F. Walker,Gao Zhang,Tian Tian,Chaoran Cheng,Zhi Wei,Sangeetha Palakurthi,Mark A. Bittinger,Hans Vitzthum,Jong Wook Kim,Jong Wook Kim,Ashley A. Merlino,Max M. Quinn,Chandrasekar Venkataramani,Joshua A. Kaplan,Andrew Portell,Prafulla C. Gokhale,Bart Phillips,Alicia Smart,Alicia Smart,Asaf Rotem,Robert E. Jones,Lauren Keogh,Maria Anguiano,Lance Stapleton,Zhiheng Jia,Michal Barzily-Rokni,Israel Cañadas,Tran C. Thai,Marc R. Hammond,Raven Vlahos,Eric S. Wang,Hua Zhang,Shuai Li,Glenn J. Hanna,Wei Huang,Mai P. Hoang,Adriano Piris,Jean Pierre Eliane,Anat Stemmer-Rachamimov,Lisa A. Cameron,Mei-Ju Su,Parin Shah,Benjamin Izar,Benjamin Izar,Manisha Thakuria,Manisha Thakuria,Nicole R. LeBoeuf,Nicole R. LeBoeuf,Guilherme Rabinowits,Viswanath Gunda,Sareh Parangi,James M. Cleary,Brian C. Miller,Shunsuke Kitajima,Rohit Thummalapalli,Benchun Miao,Thanh U. Barbie,Vivek Sivathanu,Joshua A. Wong,William G. Richards,Raphael Bueno,Charles H. Yoon,Juan J. Miret,Meenhard Herlyn,Levi A. Garraway,Eliezer M. Van Allen,Eliezer M. Van Allen,Gordon J. Freeman,Paul Kirschmeier,Jochen H. Lorch,Patrick A. Ott,F. Stephen Hodi,Keith T. Flaherty,Roger D. Kamm,Genevieve M. Boland,Kwok-Kin Wong,David Dornan,Cloud P. Paweletz,David A. Barbie +91 more
TL;DR: The ability to interrogate ex vivo response to PD-1 blockade using murine- and patient-derived organotypic tumor spheroids (MDOTS/PDOTS) is demonstrated, which represents a novel platform to evaluate ICB using established murine models as well as clinically relevant patient specimens.
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Integrated genomic analyses of ovarian carcinoma
Debra A. Bell,Andrew Berchuck,Michael J. Birrer,Jeremy Chien,Daniel W. Cramer,Fanny Dao,Rajiv Dhir,Philip J. DiSaia,Hani Gabra,Pat Glenn,Andrew K. Godwin,John D. Gross,Lynn C. Hartmann,M. Huang,David G. Huntsman,Mary Iacocca,Marcin Imielinski,Steve E. Kalloger,Beth Y. Karlan,Beth Y. Karlan,Douglas A. Levine,Douglas A. Levine,Douglas A. Levine,Gordon B. Mills,Gordon B. Mills,Carl Morrison,David G. Mutch,Narciso Olvera,Sandra Orsulic,Kay J. Park,Nicholas J. Petrelli,Brenda Rabeno,Janet S. Rader,Branimir I. Sikic,Karen Smith-McCune,Anil K. Sood,David D.L. Bowtell,Robert Penny,Joseph R. Testa,Kyle Chang,Huyen Dinh,J. A. Drummond,G. Fowler,Preethi H. Gunaratne,A. C. Hawes,C. L. Kovar,L. R. Lewis,M. B. Morgan,I. F. Newsham,J. Santibanez,Jeffrey G. Reid,L. R. Trevino,Yue Wu,M. Wang,Donna M. Muzny,D. A. Wheeler,Richard A. Gibbs,Gad Getz,Gad Getz,Michael S. Lawrence,Michael S. Lawrence,Kristian Cibulskis,Kristian Cibulskis,Andrey Sivachenko,C. Sougnez,Douglas Voet,Douglas Voet,Jane Wilkinson,Toby Bloom,Kristin G. Ardlie,Kristin G. Ardlie,T. Fennell,Jennifer Baldwin,S. Gabriel,Eric S. Lander,Li Ding,Robert S. Fulton,Daniel C. Koboldt,Michael D. McLellan,Todd Wylie,Jason Walker,M. O'Laughlin,D. J. Dooling,Linnea Fulton,R. Abbott,N. D. Dees,Qizhou Zhang,Cyriac Kandoth,Michael C. Wendl,William Schierding,D. Shen,Chris Harris,Hayden R. Schmidt,Joelle Kalicki,K. D. Delehaunty,Catrina Fronick,Ryan Demeter,L. Cook,J. W. Wallis,L. Lin,Vincent Magrini,J. S. Hodges,James M. Eldred,S. M. Smith,Craig Pohl,Fabio Vandin,Benjamin J. Raphael,George M. Weinstock,Elaine R. Mardis,Richard K. Wilson,Matthew Meyerson,Wendy Winckler,R. G.W. Verhaak,Suzie Carter,Craig H. Mermel,G. Saksena,G. Saksena,H. Nguyen,R. C. Onofrio,D. Hubbard,S. Gupta,A. Crenshaw,A. H. Ramos,Lynda Chin,Lynda Chin,Alexei Protopopov,Jinghui Zhang,Jinghui Zhang,Jinghui Zhang,T. M. Kim,Ilana Perna,Y. Xiao,Hailei Zhang,Gang Ren,N. Sathiamoorthy,R. W. Park,R. W. Park,Eunjung Lee,Peter J. Park,Peter J. Park,Raju Kucherlapati,D. M. Absher,L. Waite,Gavin Sherlock,James D. Brooks,Jun Li,Jian Xu,Richard M. Myers,Peter W. Laird,L. Cope,James G. Herman,H. Shen,Daniel J. Weisenberger,Houtan Noushmehr,F. Pan,Timothy J. Triche,Benjamin P. Berman,D. J. Van Den Berg,J. Buckley,Stephen B. Baylin,Paul T. Spellman,Paul T. Spellman,Elizabeth Purdom,Pierre Neuvial,Pierre Neuvial,Henrik Bengtsson,Henrik Bengtsson,L. R. Jakkula,S. Durinck,S. Durinck,Junhong Han,Junhong Han,S. Dorton,H. Marr,Y. G. Choi,V. Wang,N. J. Wang,J. Ngai,J. G. Conboy,Bahram Parvin,H. S. Feiler,Terence P. Speed,Joe W. Gray,Joe W. Gray,N. D. Socci,Yanke Liang,Barry S. Taylor,Nikolaus Schultz,Nikolaus Schultz,L. Borsu,Alex E. Lash,Cameron Brennan,A. Viale,Chris Sander,M. Ladanyi,M. Ladanyi,Katherine A. Hoadley,Katherine A. Hoadley,S. Meng,Y. Du,Y. Du,Yigong Shi,Lulin Li,Y. J. Turman,D. Zang,E. B. Helms,S. Balu,Xiang Zhou,Jane Y. Wu,M. D. Topal,D. N. Hayes,D. N. Hayes,Charles M. Perou,Chaowei Wu,S. Shukla,A. Sivachenko,R. Jing,Yingkai Liu,M. Noble,Hannah Carter,D. Kim,Rachel Karchin,James E. Korkola,Laura M. Heiser,Raymond J. Cho,Zhi Hu,Ethan Cerami,A. Olshen,B. Reva,Yevgeniy Antipin,R. Shen,P. Mankoo,Robert L. Sheridan,Giovanni Ciriello,William K. Chang,J. A. Bernanke,David Haussler,Christopher C. Benz,Joshua M. Stuart,Stephen C. Benz,J. Z. Sanborn,Charles J. Vaske,Jieqing Zhu,Christopher Szeto,G. K. Scott,Christina Yau,Matthew D. Wilkerson,N. Zhang,Rehan Akbani,Keith A. Baggerly,W. K. Yung,John N. Weinstein,T. Shelton,Dirk Grimm,Martha Hatfield,Scott Morris,P. Yena,P. Rhodes,Mark E. Sherman,J. Paulauskis,S. Millis,A. Kahn,John M. Greene,R. Sfeir,M. A. Jensen,John W. Chen,J. Whitmore,S. Alonso,J. Jordan,A. Chu,A. Barker,Carolyn C. Compton,Greg Eley,Martin L. Ferguson,Peter Fielding,Daniela S. Gerhard,R. Myles,Carl F. Schaefer,K. R. Mills Shaw,Jim Vaught,J. B. Vockley,Peter J. Good,Mark S. Guyer,Bradley A. Ozenberger,Jane Peterson,Elizabeth J. Thomson +285 more
TL;DR: It is reported that high-grade serous ovarian cancer is characterized by TP53 mutations in almost all tumours (96%); low prevalence but statistically recurrent somatic mutations in nine further genes including NF1, BRCA1,BRCA2, RB1 and CDK12; 113 significant focal DNA copy number aberrations; and promoter methylation events involving 168 genes.
Integrated genomic analyses of ovarian carcinoma
Daphne W. Bell,Andrew Berchuck,Michael J. Birrer,Jeremy Chien,Daniel W. Cramer,Fanny Dao,Rajiv Dhir,Philip J. DiSaia,Hani Gabra,Pat Glenn,Andrew K. Godwin,John D. Gross,Lynn C. Hartmann,Mei Huang,David G. Huntsman,Mary Iacocca,Marcin Imielinski,Steve E. Kalloger,Beth Y. Karlan,Douglas A. Levine,Gordon B. Mills,Carolyn A. Morrison,David G. Mutch,Narciso Olvera,Sandra Orsulic,Kay J. Park,Nicholas J. Petrelli,Brenda Rabeno,Janet S. Rader,Branimir I. Sikic,Karen Smith-McCune,Anil K. Sood,David D.L. Bowtell,Robert Penny,Joseph R. Testa,Kyle Chang,Huyen Dinh,Jennifer Drummond,Gerald R. Fowler,Preethi H. Gunaratne,Alicia Hawes,Christie Kovar,Lora Lewis,Margaret B. Morgan,Irene Newsham,Jireh Santibanez,Jeffrey G. Reid,Lisa R. Trevino,Yuan Qing Wu,Min Wang,Donna Muzny,D Wheeler,Richard A. Gibbs,Gad Getz,Michael S. Lawrence,Kristian Cibulskis,Andrey Sivachenko,Carrie Sougnez,Douglas Voet,Jane Wilkinson,Toby Bloom,Kristin G. Ardlie,T. J. Fennell,Jennifer Baldwin,S. Gabriel,Eric S. Lander,Li Ding,Robert S. Fulton,Daniel C. Koboldt,Michael D. McLellan,Todd Wylie,Jason Walker,Michelle D O'Laughlin,David J. Dooling,Linnea Fulton,Rachel Abbott,Nathan D. Dees,Qizhou Zhang,Cyriac Kandoth,Michael C. Wendl,William Schierding,D. Shen,Chris Harris,Heather K. Schmidt,Joelle Kalicki,Kimberly D. Delehaunty,Catrina Fronick,Ryan Demeter,Linda S. Cook,John W. Wallis,Ling Lin,Vincent Magrini,Jennifer S. Hodges,James M. Eldred,Shaleigh Smith,Craig Pohl,Fabio Vandin,Benjamin J. Raphael,George M. Weinstock,Elaine R. Mardis,Richard K. Wilson,Matthew Meyerson,Wendy Winckler,Roeland Verhaak,Suzie Carter,Craig H. Mermel,Gordon Saksena,Huy V. Nguyen,Robert C. Onofrio,Diana D. Hubbard,Sonal Gupta,Andrew Crenshaw,Alex H. Ramos,Lynda Chin,Alexei Protopopov,Juinhua Zhang,T. M. Kim,Ilana Perna,Yonghong Xiao,Hailei Zhang,Gang Ren,Narayanan Sathiamoorthy,Richard W. Park,Eunjung Lee,Peter J. Park,Raju Kucherlapati,Devin Absher,Lindsay L. Waite,Gavin Sherlock,James D. Brooks,Jun Li,Jian Xu,Richard M. Myers,Peter W. Laird,Leslie Cope,James G. Herman,Hui Shen,Daniel J. Weisenberger,Houtan Noushmehr,Fei Pan,Timothy J. Triche,Benjamin P. Berman,D. J. Van Den Berg,Jonathan D. Buckley,Stephen B. Baylin,P. Spellman,Elizabeth Purdom,Pierre Neuvial,Henrik Bengtsson,Lakshmi Jakkula,Steffen Durinck,Junhong Han,Shannon Dorton,Henry Marr,Y. G. Choi,V. Wang,N. J. Wang,J. Ngai,John G. Conboy,Bahram Parvin,Heidi S. Feiler,Terence P. Speed,Joe W. Gray,Nicholas D. Socci,Yanke Liang,Barry S. Taylor,Nikolaus Schultz,Laetitia Borsu,Alex E. Lash,Cameron Brennan,Agnes Viale,Chris Sander,M. Ladanyi,Katherine A. Hoadley,Shaowu Meng,Ying Du,Yan Shi,Lulin Li,Yidi J. Turman,D. Zang,E. B. Helms,Saianand Balu,Xiang Zhou,Jane Y. Wu,Michael D. Topal,David N. Hayes,Charles M. Perou,Junihua Zhang,Chaowei Wu,Sachet A. Shukla,Andrey Sivachenko,Rui Jing,Yingkai Liu,Michael S. Noble,Hannah Carter,D. Kim,Rachel Karchin,James E. Korkola,Laura M. Heiser,Raymond J. Cho,Zhi Hu,Ethan Cerami,Adam B. Olshen,Boris Reva,Yevgeniy Antipin,Ronglai Shen,Parminder K. Mankoo,Rachael Sheridan,Giovanni Ciriello,William K. Chang,J. A. Bernanke,David Haussler,Christopher C. Benz,Joshua M. Stuart,Stephen C. Benz,John Zachary Sanborn,Charles J. Vaske,Jingchun Zhu,Christopher Szeto,Gary K. Scott,Christina Yau,Matthew D. Wilkerson,Nianxiang Zhang,Rehan Akbani,Keith A. Baggerly,W. K. Yung,John N. Weinstein,Troy Shelton,Dirk Grimm,Martha Hatfield,Shannon R. Morris,Peggy Yena,P. Rhodes,Mark E. Sherman,Joseph Paulauskis,S. Millis,Ari B. Kahn,John M. Greene,Robert Sfeir,Mark A. Jensen,John W. Chen,Jon Whitmore,Shelley Alonso,Justin T. Jordan,Anna L. Chu,Jinghui Zhang,Anna D. Barker,Carolyn C. Compton,Greg Eley,Martin L. Ferguson,Peter Fielding,Daniela S. Gerhard,R. Myles,Carl F. Schaefer,K. R. Mills Shaw,Jim Vaught,J. B. Vockley,Peter J. Good,Mark S. Guyer,Bradley A. Ozenberger,Jessica L. Peterson,E. Thomson +261 more
TL;DR: The Cancer Genome Atlas project has analyzed messenger RNA expression, microRNA expression, promoter methylation and DNA copy number in 489 high-grade serous ovarian adenocarcinomas and the DNA sequences of exons from coding genes in 316 of these tumours as mentioned in this paper.