ArticleCancer cell2023
Lymphocyte networks are dynamic cellular communities in the immunoregulatory landscape of lung adenocarcinoma.
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Article in Cancer cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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53citing papers in PubMed
14.5field-weighted citation impact, top 1% of its field
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53 citing papers in PubMed, 70 citations in OpenAlex.
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- The Dual Role of IP-10/CXCL10 in Liver Injury: From Pathogenic Mediator to Clinical Biomarker and Therapeutic Target.Drug design, development and therapy · 2026Review
- Mechanisms of T cell-mediated antitumor immunity within tertiary lymphoid structures.Frontiers in immunology · 2026Review
- Stem-like T cells: molecular regulation, functional diversity, and therapeutic implications across diseases.Journal of translational medicine · 2025Review
- CIMT 2025: Report on the 22Human vaccines & immunotherapeutics · 2025Article
- [Influence and Mechanism of Immunophenotyping on the Efficacy of Neoadjuvant Therapy in Non-small Cell Lung Cancer].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2025Article
- The diversity of CD8Nature reviews. Immunology · 2025Review
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Authors and funding
18 authors at 3 institutions in 1 country.
Giorgio GagliaLaboratory of Systems Pharmacology, Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA; Ludwig Center at Harvard, Harvard Medical School, Boston, MA 02115, USA; Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Megan L BurgerDavid H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Cell, Developmental and Cancer Biology, Oregon Health & Science University, Portland, OR 97212, USA; School of Medicine, Division of Hematology and Oncology, Oregon Health & Science University, Portland, OR 97212, USA.
Cecily C RitchLaboratory of Systems Pharmacology, Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA; Ludwig Center at Harvard, Harvard Medical School, Boston, MA 02115, USA; Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Danae RammosLaboratory of Systems Pharmacology, Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA; Ludwig Center at Harvard, Harvard Medical School, Boston, MA 02115, USA; Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Yang DaiLaboratory of Systems Pharmacology, Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA; Ludwig Center at Harvard, Harvard Medical School, Boston, MA 02115, USA; Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Grace E CrosslandDavid H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Sara Z TavanaDavid H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Simon WarcholLaboratory of Systems Pharmacology, Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA; School of Engineering and Applied Sciences, Harvard University, Boston, MA 02134, USA.
Alex M JaegerDavid H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Santiago NaranjoDavid H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Shannon CoyLaboratory of Systems Pharmacology, Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA; Ludwig Center at Harvard, Harvard Medical School, Boston, MA 02115, USA; Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Ajit J NirmalLaboratory of Systems Pharmacology, Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.
Robert KruegerLaboratory of Systems Pharmacology, Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA; School of Engineering and Applied Sciences, Harvard University, Boston, MA 02134, USA.
Jia-Ren LinLaboratory of Systems Pharmacology, Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA; Ludwig Center at Harvard, Harvard Medical School, Boston, MA 02115, USA.
Hanspeter PfisterSchool of Engineering and Applied Sciences, Harvard University, Boston, MA 02134, USA.
Peter K SorgerLaboratory of Systems Pharmacology, Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA; Ludwig Center at Harvard, Harvard Medical School, Boston, MA 02115, USA.
Tyler JacksDavid H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Sandro SantagataLaboratory of Systems Pharmacology, Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA; Ludwig Center at Harvard, Harvard Medical School, Boston, MA 02115, USA; Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. Electronic address: ssantagata@bics.bwh.harvard.edu.
Harvard University · USMassachusetts Institute of Technology · USOregon Health & Science University · US
Funding
VectorP30CA006516 · NCI · DANA-FARBER CANCER INSTITUTE · PI JENNIFER W MACK · 1985 to 2026
$330.6MVIRUS PRODUCTION COREP30CA014051 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI Paula T Hammond · 1985 to 2026
$93.9MVASCULAR, PULMONARY AND RENAL INJURYT32HL007627 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI GIMBRONE, MICHAEL A, MITCHELL, RICHARD N · 1985 to 2019
$12.7MTRAINING GRANT IN GENETICST32GM007748 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI Anne O'Donnell-Luria, Louise Wilkins-Haug · 1985 to 2026
$12.0MSystems Pharmacology of Therapeutic and Adverse Responses to ImmuneCheckpoint and Small Molecule DrugsU54CA225088 · NCI · HARVARD MEDICAL SCHOOL · PI HAIGIS, MARCIA · 2018 to 2022
$10.8MPre-cancer atlases of cutaneous and hematologic origin (PATCH Center)U2CCA233262 · NCI · HARVARD MEDICAL SCHOOL · PI SANTAGATA, SANDRO, SORGER, PETER KARL · 2018 to 2023
$8.7MInvestigating the HSF1 Cancer NetworkR01CA194005 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI SANTAGATA, SANDRO · 2016 to 2020
$2.0MAdvancing technologies for the collection and analysis of high dimensional immunoprofiles and tumor imagesR50CA274277 · NCI · HARVARD MEDICAL SCHOOL · PI Jia-Ren Lin · 2022 to 2026
$879kExploring the impact of HSP90 inhibition on antigen presentation and anti-tumor immune responsesR00CA241072 · NCI · H. LEE MOFFITT CANCER CTR & RES INST · PI JAEGER, ALEX · 2022 to 2024
$742kExploring the impact of HSP90 inhibition on antigen presentation and anti-tumor immune responsesK99CA241072 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI JAEGER, ALEX · 2020 to 2021
$300kIntegrative Prediction of Therapeutic Response in T-cell Lymphoma by Omic and Spatial ModelingK99CA256497 · NCI · DANA-FARBER CANCER INST · PI NIRMAL, AJIT JOHNSON · 2021 to 2022
$272kHighly Multiplexed Analysis of Solid Tumors and Liquid Tissues by Cyclic ImmunofluorescenceR41CA224503 · NCI · RARECYTE, INC. · PI KALDJIAN, ERIC · 2018 to 2018
$224kNCI NIH HHS K99 CA241072NCI NIH HHS K99 CA256497NCI NIH HHS P30 CA006516NCI NIH HHS P30 CA014051NCI NIH HHS R00 CA241072NCI NIH HHS R01 CA194005NCI NIH HHS R41 CA224503NCI NIH HHS R50 CA274277NCI NIH HHS U2C CA233262NCI NIH HHS U54 CA225088NHLBI NIH HHS T32 HL007627NIGMS NIH HHS T32 GM007748
Abstract
Lymphocytes are key for immune surveillance of tumors, but our understanding of the spatial organization and physical interactions that facilitate lymphocyte anti-cancer functions is limited. We used multiplexed imaging, quantitative spatial analysis, and machine learning to create high-definition maps of lung tumors from a Kras/Trp53-mutant mouse model and human resections. Networks of interacting lymphocytes ("lymphonets") emerged as a distinctive feature of the anti-cancer immune response. Lymphonets nucleated from small T cell clusters and incorporated B cells with increasing size. CXCR3-mediated trafficking modulated lymphonet size and number, but T cell antigen expression directed intratumoral localization. Lymphonets preferentially harbored TCF1
Indexed as
Adenocarcinoma of LungLung NeoplasmsAnimalsCD8-Positive T-LymphocytesHumansImmunityImmunotherapyMicecancer vaccinescomputational biologyCyCIFimmunotherapylung adenocarcinomamultimodal data integrationmultiplexed imagingspatial biologyspatial profilingsystems biology
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.