Ultrasound stiffness and perfusion markers correlate with tumor volume responses to immunotherapy

by Selleckchem | Nov 02 2023

Immunotherapy has revolutionized the treatment of dozens of cancers and became a standard of care for some tumor types. However, the majority of patients do not benefit from current immunotherapeutics and many develop severe toxicities. Therefore, the identification of biomarkers to classify patients as likely responders or non-responders to immunotherapy is a timely task. Here, we test ultrasound imaging markers of tumor stiffness and perfusion. Ultrasound imaging is non-invasive and clinically available and can be used both for stiffness and perfusion evaluation. In this study, we employed syngeneic orthotopic models of two breast cancers, a fibrosarcoma and a melanoma, to demonstrate that ultrasound-derived measures of tumor stiffness and perfusion (i.e., blood volume) correlate with the efficacy of immune checkpoint inhibition (ICI) in terms of changes in primary tumor volume. To modulate tumor stiffness and perfusion and thus, get a range of therapeutic outcomes, we employed the mechanotherapeutic tranilast. Mechanotherapeutics combined with ICI are advancing through clinical trials, but biomarkers of response have not been tested until now. We found the existence of linear correlations between tumor stiffness and perfusion imaging biomarkers as well as strong linear correlations between the stiffness and perfusion markers with ICI efficacy on primary tumor growth rates. Our findings set the basis for ultrasound biomarkers predictive of ICI therapy in combination with mechanotherapeutics. STATEMENT OF SIGNIFICANCE: Hypothesis: Monitoring Tumor Microenvironment (TME) mechanical abnormalities can predict the efficacy of immune checkpoint inhibition and provide biomarkers predictive of response. Tumor stiffening and solid stress elevation are hallmarks of tumor patho-physiology in desmoplastic tumors. They induce hypo-perfusion and hypoxia by compressing tumor vessels, posing major barriers to immunotherapy. Mechanotherapeutics is a new class of drugs that target the TME to reduce stiffness and improve perfusion and oxygenation. In this study, we show that measures of stiffness and perfusion derived from ultrasound shear wave elastography and contrast enhanced ultrasound can provide biomarkers of tumor response.

Comments:

The research described focuses on the potential use of ultrasound imaging markers to identify biomarkers that can predict the response to immunotherapy in cancer patients. The authors utilized syngeneic orthotopic models of breast cancer, fibrosarcoma, and melanoma to investigate the correlation between ultrasound-derived measures of tumor stiffness and perfusion with the efficacy of immune checkpoint inhibition (ICI).

Tumor stiffness and perfusion are important factors in the tumor microenvironment (TME) and can impact the response to immunotherapy. Desmoplastic tumors, characterized by increased stiffness and solid stress, often exhibit hypo-perfusion and hypoxia due to compression of tumor vessels, which can hinder the effectiveness of immunotherapy. Mechanotherapeutics, a new class of drugs targeting the TME, aim to reduce stiffness and improve perfusion and oxygenation.

The study employed ultrasound shear wave elastography and contrast-enhanced ultrasound to measure tumor stiffness and perfusion, respectively. The researchers observed linear correlations between these imaging biomarkers and the efficacy of ICI in terms of changes in primary tumor volume. Furthermore, the authors used the mechanotherapeutic drug tranilast to modulate tumor stiffness and perfusion, obtaining a range of therapeutic outcomes.

The findings of this study suggest that ultrasound-derived measures of tumor stiffness and perfusion can serve as predictive biomarkers for the response to ICI therapy in combination with mechanotherapeutics. Monitoring TME mechanical abnormalities, such as tumor stiffening and solid stress elevation, can provide valuable insights into tumor pathophysiology and help overcome barriers to immunotherapy, such as hypo-perfusion and hypoxia.

In summary, this research highlights the potential of ultrasound imaging as a non-invasive and clinically available tool for evaluating tumor stiffness and perfusion, which may aid in the identification of patients likely to respond to immunotherapy and guide the development of personalized treatment approaches.