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In vivo tumor immune microenvironment phenotypes correlate with inflammation and vasculature to predict immunotherapy response

Author

Listed:
  • Aditi Sahu

    (Memorial Sloan Kettering Cancer Center)

  • Kivanc Kose

    (Memorial Sloan Kettering Cancer Center)

  • Lukas Kraehenbuehl

    (Memorial Sloan Kettering Cancer Center)

  • Candice Byers

    (Northeastern University
    Northeastern University)

  • Aliya Holland

    (Memorial Sloan Kettering Cancer Center)

  • Teguru Tembo

    (Memorial Sloan Kettering Cancer Center
    SUNY Downstate Health Sciences University)

  • Anthony Santella

    (Memorial Sloan Kettering Cancer Center)

  • Anabel Alfonso

    (Memorial Sloan Kettering Cancer Center)

  • Madison Li

    (Memorial Sloan Kettering Cancer Center)

  • Miguel Cordova

    (Memorial Sloan Kettering Cancer Center)

  • Melissa Gill

    (SUNY Downstate Health Sciences University
    Karolinska University Hospital Solna
    University of Alcala)

  • Christi Fox

    (Caliber Imaging and Diagnostics)

  • Salvador Gonzalez

    (University of Alcala)

  • Piyush Kumar

    (Icahn School of Medicine at Mount Sinai)

  • Amber Weiching Wang

    (ORIC Pharmaceuticals)

  • Nicholas Kurtansky

    (Memorial Sloan Kettering Cancer Center)

  • Pratik Chandrani

    (Tata Memorial Hospital)

  • Shen Yin

    (Memorial Sloan Kettering Cancer Center)

  • Paras Mehta

    (Memorial Sloan Kettering Cancer Center)

  • Cristian Navarrete-Dechent

    (Memorial Sloan Kettering Cancer Center
    Pontificia Universidad Católica de Chile)

  • Gary Peterson

    (Memorial Sloan Kettering Cancer Center)

  • Kimeil King

    (Memorial Sloan Kettering Cancer Center)

  • Stephen Dusza

    (Memorial Sloan Kettering Cancer Center)

  • Ning Yang

    (Memorial Sloan Kettering Cancer Center)

  • Shuaitong Liu

    (Memorial Sloan Kettering Cancer Center)

  • William Phillips

    (Memorial Sloan Kettering Cancer Center)

  • Pascale Guitera

    (Sydney Melanoma Diagnostic Center
    Melanoma Institute Australia)

  • Anthony Rossi

    (Memorial Sloan Kettering Cancer Center)

  • Allan Halpern

    (Memorial Sloan Kettering Cancer Center)

  • Liang Deng

    (Memorial Sloan Kettering Cancer Center
    Weill Cornell Medicine)

  • Melissa Pulitzer

    (Memorial Sloan Kettering Cancer Center)

  • Ashfaq Marghoob

    (Memorial Sloan Kettering Cancer Center)

  • Chih-Shan Jason Chen

    (Memorial Sloan Kettering Cancer Center)

  • Taha Merghoub

    (Memorial Sloan Kettering Cancer Center
    Memorial Sloan Kettering Cancer Center
    Weill Cornell Medicine)

  • Milind Rajadhyaksha

    (Memorial Sloan Kettering Cancer Center)

Abstract

Response to immunotherapies can be variable and unpredictable. Pathology-based phenotyping of tumors into ‘hot’ and ‘cold’ is static, relying solely on T-cell infiltration in single-time single-site biopsies, resulting in suboptimal treatment response prediction. Dynamic vascular events (tumor angiogenesis, leukocyte trafficking) within tumor immune microenvironment (TiME) also influence anti-tumor immunity and treatment response. Here, we report dynamic cellular-level TiME phenotyping in vivo that combines inflammation profiles with vascular features through non-invasive reflectance confocal microscopic imaging. In skin cancer patients, we demonstrate three main TiME phenotypes that correlate with gene and protein expression, and response to toll-like receptor agonist immune-therapy. Notably, phenotypes with high inflammation associate with immunostimulatory signatures and those with high vasculature with angiogenic and endothelial anergy signatures. Moreover, phenotypes with high inflammation and low vasculature demonstrate the best treatment response. This non-invasive in vivo phenotyping approach integrating dynamic vasculature with inflammation serves as a reliable predictor of response to topical immune-therapy in patients.

Suggested Citation

  • Aditi Sahu & Kivanc Kose & Lukas Kraehenbuehl & Candice Byers & Aliya Holland & Teguru Tembo & Anthony Santella & Anabel Alfonso & Madison Li & Miguel Cordova & Melissa Gill & Christi Fox & Salvador G, 2022. "In vivo tumor immune microenvironment phenotypes correlate with inflammation and vasculature to predict immunotherapy response," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32738-7
    DOI: 10.1038/s41467-022-32738-7
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