Date of Graduation

12-2021

Document Type

Thesis

Degree Name

Master of Science in Biomedical Engineering (MSBME)

Degree Level

Graduate

Department

Biomedical Engineering

Advisor

Narasimhan Rajaram

Committee Member

Timothy Muldoon

Second Committee Member

Young H. Song

Keywords

colon cancer, Diffuse reflectance spectroscopy, Immune checkpoint inhibitor, in vivo, random forest

Abstract

Immune checkpoint drugs have completely changed the way people treat metastatic melanoma and non-small-cell lung cancer. While the impacts of these immunological checkpoints and their suppression on T cell function are well characterized, their consequences on the tumor microenvironment are not. In a CT26 mouse colorectal cancer model, we employed diffuse reflectance spectroscopy to track in vivo tumor microenvironmental alterations in response to immune checkpoint inhibitors. On three separate days, animals bearing CT26 tumor xenografts were given anti-PD-L1, anti-CTLA-4, a combination of both inhibitors, and isotype control. Within the first 6 days, monotherapy with either anti-PD-L1 or anti-CTLA-4 resulted in a significant increase in tumor vascular oxygenation. The combination of increased oxygenated hemoglobin and decreased deoxygenated hemoglobin caused reoxygenation in anti-CTLA-4-treated tumors, indicating a probable alteration in tumor oxygen consumption following treatment. Reoxygenation was predominantly owing to a rise in oxygenated hemoglobin within a minor change in deoxygenated hemoglobin in anti-PD-L1-treated tumors, indicating a potential increase in tumor perfusion. Except for tumors treated with both inhibitors in combination, none of the other tumor groups demonstrated any reduction in tumor volume. Following therapy, there were no significant changes in tumor oxygenation in the combination treatment group. These results show that diffuse reflectance spectroscopy may detect changes in the tumor microenvironment after immunotherapy and that such non-invasive approaches can be used to predict early tumor response to immune checkpoint inhibitors

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