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MCT4-dependent lactate secretion suppresses antitumor immunity in LKB1-deficient lung adenocarcinoma
Affiliation:1. Department of Thoracic/Head and Neck Medical Oncology, Houston, TX, USA;2. Department of Genomic Medicine, Houston, TX, USA;3. Department of Bioinformatics and Computational Biology, Houston, TX, USA;4. Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA;5. Broad Institute of MIT and Harvard, Cambridge, MA, USA;6. Center for Cancer Research, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA;7. Ludwig Collaborative and Swim Across America Laboratory, MSK, New York, NY, USA;8. Division of Hematology & Medical Oncology, Laura and Isaac Perlmutter Cancer Center, New York University Langone Medical Center, New York, NY, USA;9. Children’s Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA;10. Hamon Center for Therapeutic Oncology Research, UT Southwestern Medical Center, Dallas, TX, USA;11. Department of Medicine, Division of Hematology/Oncology, Massachusetts General Hospital Cancer Center, Boston, MA, USA;12. Center for Thoracic Cancers, Massachusetts General Hospital, Boston, MA, USA;1. Immunology, Microenvironment and Metastasis Program, The Wistar Institute, Philadelphia, PA 19104, USA;2. Department of Experimental Therapeutics, University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA;3. Department of Pharmacy and Biotechnology, University of Bologna, 40126, Bologna, Italy;4. Molecular and Cellular Oncogenesis Program, The Wistar Institute, Philadelphia, PA 19104, USA;5. Bioinformatics Facility, The Wistar Institute, Philadelphia, PA 19104, USA;6. Gene Expression and Regulation Program, The Wistar Institute, Philadelphia, PA 19104, USA;7. Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA;8. Department of Obstetrics and Gynecology, Penn Ovarian Cancer Research Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA;1. Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA;2. Department of Otorhinolaryngology, Saarland University, Homburg, Germany;3. Breast Cancer Center, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA;1. Division of Molecular Pathology, the Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, 1066CX Amsterdam, the Netherlands;2. Oncode Institute, Amsterdam, the Netherlands;3. Department of Molecular Oncology and Immunology, the Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, 1066CX Amsterdam, the Netherlands;4. Department of Pathology, Amsterdam UMC, Vrije Universiteit Amsterdam, 1081HV Amsterdam, the Netherlands;5. Division of Tumor Biology and Immunology, Oncode Institute, the Netherlands Cancer Institute, 1066CX Amsterdam, the Netherlands;6. Cell Biology, Neurobiology and Biophysics, Department of Biology, Faculty of Science, Utrecht University, 3584CT Utrecht, the Netherlands;7. Division of Gene Regulation, the Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, 1066CX Amsterdam, the Netherlands;8. Division of Cell Biology, the Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, 1066CX Amsterdam, the Netherlands;9. Biostatistics Centre & Department of Psychosocial Research and Epidemiology, the Netherlands Cancer Institute, 1066CX Amsterdam, the Netherlands;10. Department of Human Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam UMC, 1105AZ Amsterdam, the Netherlands;11. Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and University Medical Centre (UMC), 3584CT Utrecht, the Netherlands;12. Princess Maxima Center for Pediatric Oncology, 3584CT Utrecht, the Netherlands;13. Department of Pathology, Cancer Center Amsterdam, Amsterdam University Medical Center, Amsterdam, the Netherlands;14. Divisions of Molecular Pathology and of Medical Oncology, the Netherlands Cancer Institute, 1066CX Amsterdam, the Netherlands;15. Department of Pathology, University Medical Center, 1081HV Utrecht, the Netherlands;16. Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584CT Utrecht, the Netherlands;17. Netherlands Proteomics Center, 3584CT Utrecht, the Netherlands;1. Department of Pathology, Stanford University, Stanford, CA, USA;2. Immunology Program, Stanford University, Stanford, CA, USA;3. Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA;4. Weill Cornell Medical College, New York, NY, USA;5. Parker Institute for Cancer Immunotherapy, Memorial Sloan Kettering Cancer Center, New York, NY, USA;6. Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA;7. Antitumor Assessment Core Facility, Memorial Sloan Kettering Cancer Center, New York, NY, USA;8. Druckenmiller Center for Lung Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY, USA;9. Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA;10. Cancer Biology Program, Louis V. Gerstner Jr. Graduate School of Biomedical Sciences, Memorial Sloan Kettering Cancer Center, New York, NY, USA;11. Precision Pathology Center, Memorial Sloan Kettering Cancer Center, New York, NY, USA;12. Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA;13. Ludwig Collaborative and Swim Across America Laboratory, Memorial Sloan Kettering Cancer Center, New York, NY, USA;14. Parker Institute for Cancer Immunotherapy, San Francisco, CA, USA;15. Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA;16. Gladstone-UCSF Institute of Genomic Immunology, San Francisco, CA, USA;17. Stanford Cancer Institute, Stanford University, Stanford, CA, USA;18. Parker Institute for Cancer Immunotherapy, Stanford University, Stanford, CA, USA;19. Santa Ana Bio, Alameda, CA, USA;1. Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA;2. Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA;3. Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA;4. Department of Oncology Research BIT, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA;5. Department of Biologics Development, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA;6. Hamon Center for Therapeutic Oncology Research, Simmons Comprehensive Cancer Center, Department of Pharmacology, The University of Texas Southwestern Medical Center, Dallas, TX, USA;7. Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX, USA;8. Division of Translational Genomics, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwa, Japan;9. Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA;1. CAS Key Laboratory of Tissue Microenvironment and Tumor, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Nutrition and Health, Shanghai Jiao Tong University School of Medicine (SJTUSM) & Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China;2. Department of Urology, Institute of Surgery Research, Daping Hospital, Army Medical University, Chongqing 400042, China;3. Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China;4. State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China;5. Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China;6. Department of Urology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, 301 Yanchang Road, Shanghai 200072, China;7. Department of Obstetrics, Gynecology and Pediatrics, West China Second University Hospital, Sichuan University, 20 Renmin South Road, Chengdu 610041, China;8. Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, 101 Longmian Avenue, Nanjing, Jiangsu 211166, China;9. State Key Laboratories for Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing 100193, China
Abstract:
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  • Keywords:LKB1  lung adenocarcinoma  PD-1  immunotherapy resistance  lactate  MCT4  T cell activation  macrophage polarization  metabolism
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