Assessment of early biochemical alterations in tumors

Researchers at the University of Arkansas have shown the first use of a non-invasive optical technique to determine complex biochemical changes in cancers treated with immunotherapy.

“We show that optical spectroscopy allows sensitive detection of early changes in the biomolecular composition of tumors,” said Narasimhan Rajaram, associate professor of biomedical engineering. “This is important because these changes predict the response to immunotherapy with immune checkpoint inhibitors. Thus, our work is the first step in determining whether Raman spectroscopy can identify responders and non-responders to treatment early in treatment. “

Immune checkpoints act as brakes on the immune system to ensure that the body’s immune response is commensurate with the level of threat detected. Immune checkpoint inhibitors effectively suppress these brakes and release the body’s immune system against cancer cells.

The study, published in Research against cancer, a journal of the American Association for Cancer Research, describes the use of Raman spectroscopy to determine the molecular composition of colon cancer tumors in mice treated with two types of immunotherapy drugs currently used in the clinical treatment of patients.

Raman spectroscopy uses optical fibers to direct near infrared laser light to biological tissue. The Raman signal scattered from the tissue is particularly sensitive to the molecular composition of the tissue.

For this study, the researchers used machine learning approaches to train hundreds of Raman datasets acquired from colon cancer tumors treated with different immunotherapy drugs. They then tested the data for each tumor against the overall data set to determine the difference between tumors that had received various types of immunotherapy and tumors that had received no therapy.

The Raman technique has demonstrated sensitive detection of early changes in the biomolecular composition of tumors and a differentiated tumor response to different treatments. The changes detected by the non-invasive Raman probe were consistent with changes described by detailed tissue analysis, the researchers found.

Unlike other forms of cancer treatment, immunotherapy does not cause an immediate and predictable reduction in tumor size, and there is currently no precise method for determining response to treatment in patients. Only a small group of patients benefit from immunotherapy, and there are serious side effects associated with specific combinations of immunotherapy.

Rajaram has partnered with Ishan Barman, Associate Professor of Mechanical Engineering at Johns Hopkins University, and Alan J. Tackett, Associate Director of the Winthrop P. Rockefeller Cancer Institute and Professor of Biochemistry at the University of Arkansas for medical sciences. Joel Rodriguez Troncoso, a graduate student in biomedical engineering at the U of A, and Santosh Kumar Paidi at Johns Hopkins University were the main authors of the article.

In addition to Rodriguez Troncoso and Kumar Paidi, the co-authors of the article were Paola Monterroso Diaz, Jesse D. Ivers and David E. Lee from the University of Arkansas, Piyush Raj from Johns Hopkins University and Nathan L. Avaritt, Allen J Gies, Charles M. Quick, and Stephanie D. Byrum of the University of Arkansas for Medical Sciences.

This research was supported by the Society of Laboratory Automation and Screening Graduate Fellowship, Arkansas Biomedical Research Excellence Networks IDeA, Winthrop P. Rockefeller Cancer Institute, and National Cancer Grants Institute, of the National Institute of Biomedical Imaging and Bioengineering, and the National Institute of General Medical Sciences.

Reference: Paidi SK, Troncoso JR, Raj P, et al. Raman spectroscopy and machine learning reveal early tumor microenvironmental changes induced by immunotherapy. Cancer Res. 2021. https://cancerres.aacrjournals.org/content/early/2021/09/28/0008-5472.CAN-21-1438

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