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Tumor draining lymph nodes connected to cold triple-negative breast cancers are characterized by Th2-associated microenvironment

Author

Listed:
  • Weihua Guo

    (Beckman Research Institute, City of Hope)

  • Jiayi Tan

    (Beckman Research Institute, City of Hope
    City of Hope Comprehensive Cancer Center)

  • Lei Wang

    (Beckman Research Institute, City of Hope
    Shenzhen University Medical School)

  • Colt A. Egelston

    (Beckman Research Institute, City of Hope)

  • Diana L. Simons

    (Beckman Research Institute, City of Hope)

  • Aaron Ochoa

    (City of Hope Comprehensive Cancer Center)

  • Min Hui Lim

    (Beckman Research Institute, City of Hope
    Cleveland Clinic)

  • Lu Wang

    (University of Southern California)

  • Shawn Solomon

    (Beckman Research Institute, City of Hope)

  • James Waisman

    (City of Hope)

  • Christina H. Wei

    (City of Hope
    Los Angeles General Medical Center)

  • Caroline Hoffmann

    (Beckman Research Institute, City of Hope
    Inc.)

  • Joo Song

    (City of Hope)

  • Daniel Schmolze

    (City of Hope)

  • Peter P. Lee

    (Beckman Research Institute, City of Hope)

Abstract

Tumor draining lymph nodes (TDLN) represent a key component of the tumor-immunity cycle. There are few studies describing how TDLNs impact lymphocyte infiltration into tumors. Here we directly compare tumor-free TDLNs draining “cold” and “hot” human triple negative breast cancers (TDLNCold and TDLNHot). Using machine-learning-based self-correlation analysis of immune gene expression, we find unbalanced intranodal regulations within TDLNCold. Two gene pairs (TBX21/GATA3-CXCR1) with opposite correlations suggest preferential priming of T helper 2 (Th2) cells by mature dendritic cells (DC) within TDLNCold. This is validated by multiplex immunofluorescent staining, identifying more mature-DC-Th2 spatial clusters within TDLNCold versus TDLNHot. Associated with this Th2 priming preference, more IL4 producing mast cells (MC) are found within sinus regions of TDLNCold. Downstream, Th2-associated fibrotic TME is found in paired cold tumors with increased Th2/T-helper-1-cell (Th1) ratio, upregulated fibrosis growth factors, and stromal enrichment of cancer associated fibroblasts. These findings are further confirmed in a validation cohort and public genomic data. Our results reveal a potential role of IL4+ MCs within TDLNs, associated with Th2 polarization and reduced immune infiltration into tumors.

Suggested Citation

  • Weihua Guo & Jiayi Tan & Lei Wang & Colt A. Egelston & Diana L. Simons & Aaron Ochoa & Min Hui Lim & Lu Wang & Shawn Solomon & James Waisman & Christina H. Wei & Caroline Hoffmann & Joo Song & Daniel , 2024. "Tumor draining lymph nodes connected to cold triple-negative breast cancers are characterized by Th2-associated microenvironment," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-52577-y
    DOI: 10.1038/s41467-024-52577-y
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    1. Christina Curtis & Sohrab P. Shah & Suet-Feung Chin & Gulisa Turashvili & Oscar M. Rueda & Mark J. Dunning & Doug Speed & Andy G. Lynch & Shamith Samarajiwa & Yinyin Yuan & Stefan Gräf & Gavin Ha & Gh, 2012. "The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups," Nature, Nature, vol. 486(7403), pages 346-352, June.
    2. Birk Diedenhofen & Jochen Musch, 2015. "cocor: A Comprehensive Solution for the Statistical Comparison of Correlations," PLOS ONE, Public Library of Science, vol. 10(4), pages 1-12, April.
    3. Gavin J. Sutton & Daniel Poppe & Rebecca K. Simmons & Kieran Walsh & Urwah Nawaz & Ryan Lister & Johann A. Gagnon-Bartsch & Irina Voineagu, 2022. "Comprehensive evaluation of deconvolution methods for human brain gene expression," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
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