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

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 Gonzalez, Piyush Kumar, Amber Weiching Wang, Nicholas Kurtansky, Pratik Chandrani, Shen Yin, Paras Mehta, Cristian Navarrete-Dechent, Gary Peterson, Kimeil King, Stephen Dusza, Ning Yang, Shuaitong Liu, William Phillips, Pascale Guitera, Anthony Rossi, Allan Halpern, Liang Deng, Melissa Pulitzer, Ashfaq Marghoob, Chih-Shan Jason Chen, Taha Merghoub and Milind Rajadhyaksha ()
Additional contact information
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
Aliya Holland: Memorial Sloan Kettering Cancer Center
Teguru Tembo: Memorial Sloan Kettering Cancer Center
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
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
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
Anthony Rossi: Memorial Sloan Kettering Cancer Center
Allan Halpern: Memorial Sloan Kettering Cancer Center
Liang Deng: Memorial Sloan Kettering Cancer Center
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
Milind Rajadhyaksha: Memorial Sloan Kettering Cancer Center

Nature Communications, 2022, vol. 13, issue 1, 1-19

Abstract: 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.

Date: 2022
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32738-7

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DOI: 10.1038/s41467-022-32738-7

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