ArticleNature communications2023
Germline modifiers of the tumor immune microenvironment implicate drivers of cancer risk and immunotherapy response.
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Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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36citing papers in PubMed
16.1field-weighted citation impact, top 1% of its field
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Who cites it
36 citing papers in PubMed, 62 citations in OpenAlex.
- Review
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- Pan-cancer analysis of single-cell profiles with polygenic signals reveals genetic influences on tumor immunity across cancers.Communications biology · 2026Article
- The contribution of rare germline variants to the immune landscape of breast cancer.Genome medicine · 2026Article
- Relative leukocyte telomere length and the risk of lung cancer progression in individuals with pulmonary nodules.BMC medicine · 2026Article
- Immune gene diversity and STING1 variants in shaping cancer immunity across different genetic ancestry populations.Cell reports · 2026Article
- NeoPrecis: enhancing immunotherapy response prediction through integration of qualified immunogenicity and clonality-aware neoantigen landscapes.Nature communications · 2026Article
- Review
- Regulatory polymorphisms ofJournal for immunotherapy of cancer · 2025Article
- NeoPrecis: Enhancing Immunotherapy Response Prediction through Integration of Qualified Immunogenicity and Clonality-Aware Neoantigen Landscapes.bioRxiv : the preprint server for biology · 2025Article
- Comprehensive molecular impact mapping of common and rare variants at GWAS loci.bioRxiv : the preprint server for biology · 2025Article
- Mapping the genetic landscape establishing a tumor immune microenvironment favorable for anti-PD-1 response.Cell reports · 2025Article
- VADEr: Vision Transformer-Inspired Framework for Polygenic Risk Reveals Underlying Genetic Heterogeneity in Prostate Cancer.medRxiv : the preprint server for health sciences · 2025Article
- Navigating established and emerging biomarkers for immune checkpoint inhibitor therapy.Cancer cell · 2025Review
- Beneficial Probiotics with New Cancer Therapies for Improved Treatment of Hepatocellular Carcinoma.Diseases (Basel, Switzerland) · 2025Review
- To be or low TMB (tumor mutational burden).Translational cancer research · 2025Article
- Advances in the understanding and therapeutic manipulation of cancer immune responsiveness: a Society for Immunotherapy of Cancer (SITC) review.Journal for immunotherapy of cancer · 2025Review
- Stochastic modeling of single-cell gene expression adaptation reveals non-genomic contribution to evolution of tumor subclones.Cell systems · 2025Article
- S100A proteins show a spatial distribution of inflammation associated with the glioblastoma microenvironment architecture.Theranostics · 2025Article
- Relationship between single-nucleotide polymorphisms and cancer immunotherapy efficacy and toxicity: a systematic review.Frontiers in oncology · 2025Review
Corrections and comments
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Authors and funding
29 authors at 5 institutions in 1 country.
Meghana PagadalaBiomedical Sciences Program, University of California San Diego, La Jolla, CA, 92093, USA.ORCID 0000-0002-7591-6035
Timothy J SearsBioinformatics and Systems Biology Program, University of California San Diego, La Jolla, CA, 92093, USA.ORCID 0000-0002-4868-1509
Victoria H WuDepartment of Pharmacology, UCSD Moores Cancer Center, La Jolla, CA, 92093, USA.
Eva Pérez-GuijarroLaboratory of Cancer Biology and Genetics, National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD, 20892, USA.ORCID 0000-0003-2570-7697
Hyo KimUndergraduate Bioengineering Program, Jacobs School of Engineering, University of California San Diego, La Jolla, CA, 92093, USA.
Andrea CastroBioinformatics and Systems Biology Program, University of California San Diego, La Jolla, CA, 92093, USA.
James V TalwarBioinformatics and Systems Biology Program, University of California San Diego, La Jolla, CA, 92093, USA.ORCID 0000-0002-9520-1950
Cristian Gonzalez-ColinLa Jolla Institute for Immunology, La Jolla, CA, 92037, USA.
Steven CaoDivision of Epidemiology, Herbert Wertheim School of Public Health and Human Longevity Science, University of California San Diego, La Jolla, CA, 92093, USA.
Benjamin J SchmiedelLa Jolla Institute for Immunology, La Jolla, CA, 92037, USA.ORCID 0000-0002-9103-9378
Shervin GoudarziCanyon Crest Academy, San Diego, CA, 92130, USA.
Divya KiraniUndergraduate Biology and Bioinformatics Program, University of California San Diego, La Jolla, CA, 92093, USA.ORCID 0000-0001-5540-465X
Jessica AuBioinformatics and Systems Biology Program, University of California San Diego, La Jolla, CA, 92093, USA.ORCID 0000-0002-5043-2245
Tongwu ZhangDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD, 20892, USA.ORCID 0000-0003-2124-2706
Teresa LandiDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD, 20892, USA.ORCID 0000-0003-4507-329X
Rany M SalemDivision of Epidemiology, Herbert Wertheim School of Public Health and Human Longevity Science, University of California San Diego, La Jolla, CA, 92093, USA.ORCID 0000-0001-8816-6862
Gerald P MorrisDepartment of Pathology, University of California San Diego, La Jolla, CA, 92093, USA.ORCID 0000-0002-1097-4453
Olivier HarismendyBioinformatics and Systems Biology Program, University of California San Diego, La Jolla, CA, 92093, USA.
Sandip Pravin PatelCenter for Personalized Cancer Therapy, Division of Hematology and Oncology, UC San Diego Moores Cancer Center, San Diego, CA, 92037, USA.
Ludmil B AlexandrovDepartment of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, 92093, USA.
Jill P MesirovMoores Cancer Center, University of California San Diego, La Jolla, CA, 92093, USA.
Maurizio ZanettiMoores Cancer Center, University of California San Diego, La Jolla, CA, 92093, USA.
Chi-Ping DayLaboratory of Cancer Biology and Genetics, National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD, 20892, USA.ORCID 0000-0001-5200-2372
Chun Chieh FanCenter for Population Neuroscience and Genetics, Laureate Institute for Brain Research, Tulsa, OK, 74136, USA.ORCID 0000-0001-9437-2128
Wesley K ThompsonDivision of Biostatistics, Herbert Wertheim School of Public Health and Human Longevity Science, University of California San Diego, La Jolla, CA, 92093, USA.
Glenn MerlinoLaboratory of Cancer Biology and Genetics, National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD, 20892, USA.
J Silvio GutkindDepartment of Pharmacology, UCSD Moores Cancer Center, La Jolla, CA, 92093, USA.
Pandurangan VijayanandLa Jolla Institute for Immunology, La Jolla, CA, 92037, USA.ORCID 0000-0001-7067-9723
Hannah CarterMoores Cancer Center, University of California San Diego, La Jolla, CA, 92093, USA. hkcarter@health.ucsd.edu.ORCID 0000-0002-1729-2463
University of California San Diego · USNational Institutes of Health · USLa Jolla Institute for Immunology · USMoores Cancer CenterUC San Diego Health System · US
Funding
Targeting the p53 pathway for reversal of oral premalignancyP50CA097007 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI MYERS, JEFFREY NICHOLAS · 2002 to 2012
$26.1MUT M.D. Anderson Cancer Center SPORE in MelanomaP50CA093459 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI GRIMM, ELIZABETH A · 2004 to 2014
$23.7MGENETIC SUSCEPTIBILITY TO CANCER IN MULTIETHNIC COHORTSR01CA063464 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI HENDERSON, BRIAN E · 2001 to 2005
$23.2MMultiethnic Cohort Study of Diet and CancerR37CA054281 · NCI · UNIVERSITY OF HAWAII AT MANOA · PI KOLONEL, LAURENCE N. · 2003 to 2012
$23.2MResearch Resources: Epigenomic and Transcriptomic Profiles of Human Immune CellsR24AI108564 · NIAID · LA JOLLA INSTITUTE FOR IMMUNOLOGY · PI MITCHELL KRONENBERG, Bjoern Peters · 2014 to 2026
$12.1MCharacterizing Genetic Susceptibility to Breast and Prostate Cancer; the BPC3U01CA098758 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI HENDERSON, BRIAN E · 2003 to 2010
$11.0MEpidemiological and Clinical Translational Studies Post Genome-Wide AssociationU19CA148537 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI EASTON, DOUGLAS FREDERICK, EELES, ROSALIND · 2010 to 2014
$10.4MPredoctoral and Postdoctoral Training in Cancer Cell BiologyT32CA067754 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI JEAN Y.J. WANG · 1995 to 2026
$6.5MMolecular Epidemiology of Head and Neck CancerR01ES011740 · NIEHS · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI WEI, QINGYI · 2001 to 2012
$6.3MElucidating the molecular and contextual basis for IDLE ultralow risk lesions and the tumor immune microenvironment of high risk in situ and invasive breast cancersU01CA196406 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BOROWSKY, ALEXANDER D, ESSERMAN, LAURA J · 2015 to 2020
$5.8MThe Integrative Genomics Viewer (IGV) for Cancer ResearchU24CA258406 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI JILL P. MESIROV, James Thomas Robinson · 2021 to 2026
$5.1MStimulating Neo-Antigen Specific T Cell Responses in Head and Neck CancersU01DE028227 · NIDCR · LA JOLLA INSTITUTE FOR IMMUNOLOGY · PI GUTKIND, JORGE SILVIO, RAO, ANJANA · 2018 to 2022
$4.6MCancer Research UK C1287/A10118Cancer Research UK C1287/A5260Cancer Research UK C16913/A6135Cancer Research UK C16913/A6835Cancer Research UK C5047/A10692Cancer Research UK C5047/A3354Cancer Research UK C5047/A7357NCI NIH HHS F30 CA247168NCI NIH HHS P50 CA093459NCI NIH HHS P50 CA097007NCI NIH HHS R01 CA054281NCI NIH HHS R01 CA063464NCI NIH HHS R01 CA133996NCI NIH HHS R01 CA220009NCI NIH HHS R01 CA247551NCI NIH HHS R01 CA269919NCI NIH HHS R37 CA054281NCI NIH HHS T32 CA067754NCI NIH HHS U01 CA063464NCI NIH HHS U01 CA098758NCI NIH HHS U01 CA196406NCI NIH HHS U01 CA253547NCI NIH HHS U19 CA148537NCI NIH HHS U24 CA258406NHLBI NIH HHS R00 HL122515NIAID NIH HHS R24 AI108564NIDCR NIH HHS U01 DE028227NIEHS NIH HHS R01 ES011740NIGMS NIH HHS T32 GM139790
Abstract
With the continued promise of immunotherapy for treating cancer, understanding how host genetics contributes to the tumor immune microenvironment (TIME) is essential to tailoring cancer screening and treatment strategies. Here, we study 1084 eQTLs affecting the TIME found through analysis of The Cancer Genome Atlas and literature curation. These TIME eQTLs are enriched in areas of active transcription, and associate with gene expression in specific immune cell subsets, such as macrophages and dendritic cells. Polygenic score models built with TIME eQTLs reproducibly stratify cancer risk, survival and immune checkpoint blockade (ICB) response across independent cohorts. To assess whether an eQTL-informed approach could reveal potential cancer immunotherapy targets, we inhibit CTSS, a gene implicated by cancer risk and ICB response-associated polygenic models; CTSS inhibition results in slowed tumor growth and extended survival in vivo. These results validate the potential of integrating germline variation and TIME characteristics for uncovering potential targets for immunotherapy.
Indexed as
ImmunotherapyNeoplasmsGerm CellsGerm-Line MutationInhibition, PsychologicalMacrophagesTumor Microenvironment
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