Evaluating immunotherapeutic outcomes in triple-negative breast cancer with a cholesterol radiotracer in mice
Evaluating the response to immune checkpoint inhibitors (ICIs) remains an unmet challenge in triple-negative breast cancer (TNBC). The requirement for cholesterol in the activation and function of T cells led us to hypothesize that quantifying cellular accumulation of this molecule could distinguish successful from ineffective checkpoint immunotherapy. To analyze accumulation of cholesterol by T cells in the immune microenvironment of breast cancer, we leveraged the PET radiotracer, eFNP-59. eFNP-59 is an analog of cholesterol that our group validated as an imaging biomarker for cholesterol uptake in preclinical models and initial human studies. In immunocompetent mouse models of TNBC, we found that elevated uptake of exogenous labeled cholesterol analogs functions as a marker for T cell activation. When comparing ICI-responsive and -nonresponsive tumors directly, uptake of fluorescent cholesterol and eFNP-59 increased in T cells from ICI-responsive tumors. We discovered that accumulation of cholesterol by T cells increased in ICI-responding tumors that received anti-PD-1 checkpoint immunotherapy. In patients with TNBC, tumors containing cycling T cells had features of cholesterol uptake and trafficking within those populations. These results suggest that uptake of exogenous cholesterol analogs by tumor-infiltrating T cells allows detection of T cell activation and has potential to assess the success of ICI therapy.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:9 |
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| Enthalten in: |
JCI insight - 9(2024), 8 vom: 19. März |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Ciavattone, Nicholas G [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 23.04.2024 Date Revised 23.04.2024 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1172/jci.insight.175320 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a Evaluating the response to immune checkpoint inhibitors (ICIs) remains an unmet challenge in triple-negative breast cancer (TNBC). The requirement for cholesterol in the activation and function of T cells led us to hypothesize that quantifying cellular accumulation of this molecule could distinguish successful from ineffective checkpoint immunotherapy. To analyze accumulation of cholesterol by T cells in the immune microenvironment of breast cancer, we leveraged the PET radiotracer, eFNP-59. eFNP-59 is an analog of cholesterol that our group validated as an imaging biomarker for cholesterol uptake in preclinical models and initial human studies. In immunocompetent mouse models of TNBC, we found that elevated uptake of exogenous labeled cholesterol analogs functions as a marker for T cell activation. When comparing ICI-responsive and -nonresponsive tumors directly, uptake of fluorescent cholesterol and eFNP-59 increased in T cells from ICI-responsive tumors. We discovered that accumulation of cholesterol by T cells increased in ICI-responding tumors that received anti-PD-1 checkpoint immunotherapy. In patients with TNBC, tumors containing cycling T cells had features of cholesterol uptake and trafficking within those populations. These results suggest that uptake of exogenous cholesterol analogs by tumor-infiltrating T cells allows detection of T cell activation and has potential to assess the success of ICI therapy | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Breast cancer | |
| 650 | 4 | |a Diagnostic imaging | |
| 650 | 4 | |a Immunology | |
| 650 | 4 | |a Immunotherapy | |
| 650 | 4 | |a Oncology | |
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| 700 | 1 | |a Farfel, Alex |e verfasserin |4 aut | |
| 700 | 1 | |a Stauff, Jenelle |e verfasserin |4 aut | |
| 700 | 1 | |a Desmond, Timothy |e verfasserin |4 aut | |
| 700 | 1 | |a Viglianti, Benjamin L |e verfasserin |4 aut | |
| 700 | 1 | |a Scott, Peter Jh |e verfasserin |4 aut | |
| 700 | 1 | |a Brooks, Allen F |e verfasserin |4 aut | |
| 700 | 1 | |a Luker, Gary D |e verfasserin |4 aut | |
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