ArticleThe Journal of experimental medicine2023
Cancer cell plasticity and MHC-II-mediated immune tolerance promote breast cancer metastasis to lymph nodes.
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Article in The Journal of experimental medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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49 citing papers in PubMed, 58 citations in OpenAlex.
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- Microbial induction of MHC-II expression in colon cancer cells overcomes immunotherapy resistance and limits metastasis.bioRxiv : the preprint server for biology · 2026Article
- Tumor cell Jagged-1 promotes regional lymphatic metastasis and predicts recurrence in node-positive breast cancer.Breast cancer research : BCR · 2026Article
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- Development and validation of an 11-CpG methylation signature-based nomogram for predicting prognosis in early-onset breast cancer.Translational cancer research · 2026Article
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- Dual role of IFNγ in reprogramming the undifferentiated pleomorphic sarcoma cell line JBT19 towards cytotoxic chemotherapy and antitumor immunity.Oncology letters · 2026Article
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- Overcoming impaired antigen presentation in tumor-draining lymph nodes facilitates immunotherapy.Journal for immunotherapy of cancer · 2025Article
- Emerging Nanozyme Strategies for Precision Breast Cancer Treatment.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Immune modulation following α and βOncoimmunology · 2025Article
- Single-cell transcriptomics of the myeloid milieu reveals an angiogenic niche in triple-negative breast cancer.Experimental & molecular medicine · 2025Article
- Overcoming impaired antigen presentation in tumor draining lymph nodes facilitates immunotherapy.bioRxiv : the preprint server for biology · 2025Article
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Authors and funding
19 authors at 4 institutions in 1 country.
Pin-Ji Lei *Department of Radiation Oncology, Edwin L. Steele Laboratories, Massachusetts General Hospital Cancer Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.ORCID 0000-0003-2539-5179
Ethel R Pereira *Department of Radiation Oncology, Edwin L. Steele Laboratories, Massachusetts General Hospital Cancer Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.ORCID 0000-0003-0562-4536
Patrik AnderssonDepartment of Radiation Oncology, Edwin L. Steele Laboratories, Massachusetts General Hospital Cancer Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-8454-3963
Zohreh AmoozgarDepartment of Radiation Oncology, Edwin L. Steele Laboratories, Massachusetts General Hospital Cancer Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.ORCID 0000-0001-8285-8024
Jan Willem Van WijnbergenDepartment of Radiation Oncology, Edwin L. Steele Laboratories, Massachusetts General Hospital Cancer Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.ORCID 0000-0003-2828-321X
Meghan J O'MeliaDepartment of Radiation Oncology, Edwin L. Steele Laboratories, Massachusetts General Hospital Cancer Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.ORCID 0000-0003-2223-1849
Hengbo ZhouDepartment of Radiation Oncology, Edwin L. Steele Laboratories, Massachusetts General Hospital Cancer Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-9948-7909
Sampurna ChatterjeeDepartment of Radiation Oncology, Edwin L. Steele Laboratories, Massachusetts General Hospital Cancer Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.ORCID 0000-0003-0850-0328
William W HoDepartment of Radiation Oncology, Edwin L. Steele Laboratories, Massachusetts General Hospital Cancer Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-1272-8184
Jessica M PosadaDepartment of Radiation Oncology, Edwin L. Steele Laboratories, Massachusetts General Hospital Cancer Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-9056-0735
Ashwin S KumarDepartment of Radiation Oncology, Edwin L. Steele Laboratories, Massachusetts General Hospital Cancer Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.ORCID 0000-0003-3251-9977
Satoru MoritaDepartment of Radiation Oncology, Edwin L. Steele Laboratories, Massachusetts General Hospital Cancer Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-5551-8662
Lutz MenzelDepartment of Radiation Oncology, Edwin L. Steele Laboratories, Massachusetts General Hospital Cancer Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-3816-6255
Charlie ChungCold Spring Harbor Laboratory , Cold Spring Harbor, NY, USA.ORCID 0000-0003-1566-9498
Ilgin ErginCold Spring Harbor Laboratory , Cold Spring Harbor, NY, USA.ORCID 0000-0002-0007-6502
Dennis JonesDepartment of Pathology and Laboratory Medicine, School of Medicine, Boston University, Boston, MA, USA.ORCID 0000-0002-1401-9701
Peigen HuangDepartment of Radiation Oncology, Edwin L. Steele Laboratories, Massachusetts General Hospital Cancer Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-3184-6493
Semir BeyazCold Spring Harbor Laboratory , Cold Spring Harbor, NY, USA.ORCID 0000-0003-4730-4012
Timothy P PaderaDepartment of Radiation Oncology, Edwin L. Steele Laboratories, Massachusetts General Hospital Cancer Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-3453-9384
Harvard University · USCold Spring Harbor Laboratory · USBoston University · USBrigham and Women's Hospital · US
Funding
Single-Cell Biology Shared ResourceP30CA045508 · NCI · COLD SPRING HARBOR LABORATORY · PI Jessica Tollkuhn · 1987 to 2026
$118.9MVASCULAR, PULMONARY AND RENAL INJURYT32HL007627 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI GIMBRONE, MICHAEL A, MITCHELL, RICHARD N · 1985 to 2019
$12.7MSystems biology of lymphatic transportR01HL128168 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI MUNN, LANCE L., PADERA, TIMOTHY P · 2015 to 2019
$2.9MOncopathology Training ProgramT32CA251062 · NCI · DANA-FARBER CANCER INST · PI JON C. ASTER, KATHLEEN H BURNS · 2020 to 2026
$2.4MTargeting lymph node metastases to prevent cancer progressionR01CA214913 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI PADERA, TIMOTHY P · 2017 to 2022
$2.0MTargeting lymph node metastases to block cancer progressionR01CA284372 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI TIMOTHY P PADERA · 2023 to 2026
$2.0MSystems Biology of Antigen and T-Cell Transport in Cancer ImmunotherapyR01CA284603 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI Lance L. Munn, TIMOTHY P PADERA · 2023 to 2026
$1.9MUnderstanding the mechanisms of immune suppression in lymph node metastasesK22CA230315 · NCI · BOSTON UNIVERSITY MEDICAL CAMPUS · PI JONES, DENNIS · 2018 to 2020
$566kCharacterization of lymphatic contraction during infectionR21AI097745 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI PADERA, TIMOTHY P · 2012 to 2013
$480kA mechanistic dissection of the role of Eya3 in breast cancer metastasisK00CA234940 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI ZHOU, HENGBO · 2020 to 2023
$405kEnhanced antigen-lymphocyte interactions to improve immune checkpoint blockade in breast cancerF32CA275298 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI O'MELIA, MEGHAN · 2022 to 2024
$213kNCI NIH HHS F32 CA275298NCI NIH HHS K00 CA234940NCI NIH HHS K22 CA230315NCI NIH HHS P30 CA045508NCI NIH HHS R01 CA214913NCI NIH HHS R01 CA284372NCI NIH HHS R01 CA284603NCI NIH HHS T32 CA251062NHLBI NIH HHS R01 HL128168NHLBI NIH HHS T32 HL007627NIAID NIH HHS R21 AI097745
Abstract
Tumor-draining lymph nodes (TDLNs) are important for tumor antigen-specific T cell generation and effective anticancer immune responses. However, TDLNs are often the primary site of metastasis, causing immune suppression and worse outcomes. Through cross-species single-cell RNA-Seq analysis, we identified features defining cancer cell heterogeneity, plasticity, and immune evasion during breast cancer progression and lymph node metastasis (LNM). A subset of cancer cells in the lymph nodes exhibited elevated MHC class II (MHC-II) gene expression in both mice and humans. MHC-II+ cancer cells lacked costimulatory molecule expression, leading to regulatory T cell (Treg) expansion and fewer CD4+ effector T cells in TDLNs. Genetic knockout of MHC-II reduced LNM and Treg expansion, while overexpression of the MHC-II transactivator, Ciita, worsened LNM and caused excessive Treg expansion. These findings demonstrate that cancer cell MHC-II expression promotes metastasis and immune evasion in TDLNs.
Indexed as
Breast NeoplasmsAnimalsCell PlasticityCutaneous Malignant MelanomaFemaleHumansImmune ToleranceLymphatic MetastasisLymph NodesMiceT-Lymphocytes, Regulatory
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