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Published on: February 8, 2018
Longitudinal monitoring of tumor response to immune checkpoint inhibitors using noninvasive diffuse reflectance
Joel Rodriguez Troncoso1, Paola Monterroso Diaz1, David E Lee2,3
1Department of Biomedical Engineering, University of Arkansas, Fayetteville, AR 72703, USA.
Abstract:
Immune checkpoint inhibitors have revolutionized cancer treatment. However, there are currently no methods for noninvasively and nondestructively evaluating tumor response to immune checkpoint inhibitors. We used diffuse reflectance spectroscopy to monitor in vivo tumor microenvironmental changes in response to immune checkpoint inhibitors in a CT26 murine colorectal cancer model. Mice growing CT26 tumor xenografts were treated with either anti-PD-L1, anti-CTLA-4, a combination of both inhibitors, or isotype control on 3 separate days. Monotherapy with either anti-PD-L1 or anti-CTLA-4 led to a large increase in tumor vascular oxygenation within the first 6 days. Reoxygenation in anti-CTLA-4-treated tumors was due to a combination of increased oxygenated hemoglobin and decreased deoxygenated hemoglobin, pointing to a possible change in tumor oxygen consumption following treatment. Within the anti-PD-L1-treated tumors, reoxygenation was primarily due to an increase in oxygenated hemoglobin with the minimal change in deoxygenated hemoglobin, indicative of a likely increase in tumor perfusion. The tumors in the combined treatment group did not show any significant changes in tumor oxygenation following therapy. These studies demonstrate the sensitivity of diffuse reflectance spectroscopy to tumor microenvironmental changes following immunotherapy and the potential of such non-invasive techniques to determine early tumor response to immune checkpoint inhibitors.
Insights
Diffuse reflectance spectroscopy non-invasively monitors tumor changes during cancer immunotherapy. This technique shows potential for early evaluation of treatment response to immune checkpoint inhibitors.
Area of Science:
- Oncology
- Biomedical Optics
- Immunotherapy
Background:
- Immune checkpoint inhibitors (ICIs) have transformed cancer therapy.
- Current methods for evaluating ICI response are invasive or destructive.
- Non-invasive monitoring of tumor microenvironment changes is needed.
Purpose of the Study:
- To assess diffuse reflectance spectroscopy (DRS) for non-invasive monitoring of tumor response to ICIs.
- To investigate in vivo tumor microenvironmental changes induced by anti-PD-L1 and anti-CTLA-4 therapies.
- To evaluate DRS's potential for early detection of treatment efficacy.
Main Methods:
- Utilized a CT26 murine colorectal cancer model.
- Administered anti-PD-L1, anti-CTLA-4, combination therapy, or isotype control.
- Employed diffuse reflectance spectroscopy to monitor tumor vascular oxygenation changes in vivo.
Main Results:
- Monotherapy with anti-PD-L1 or anti-CTLA-4 increased tumor vascular oxygenation within 6 days.
- Anti-CTLA-4 treatment showed increased oxygenated hemoglobin and decreased deoxygenated hemoglobin, suggesting altered oxygen consumption.
- Anti-PD-L1 treatment showed increased oxygenated hemoglobin, indicating enhanced tumor perfusion.
- Combined therapy did not yield significant changes in tumor oxygenation.
Conclusions:
- Diffuse reflectance spectroscopy is sensitive to microenvironmental changes during immunotherapy.
- DRS offers a non-invasive approach for early assessment of tumor response to ICIs.
- This technique holds promise for guiding cancer treatment decisions.
