Peripheral Systemic Response Assessment in RCC
Abstract
There are no biologic methods currently available to predict or monitor response to standard systemic treatment for patients with kidney cancer. Our prior research showed that the nutrition and energy metabolism of T cells are necessary for patients to respond to immune based therapies and control cancer cells. We found that T cells from patient’s kidney tumors were exhausted and lacked activity but that these T cells could renew their function and activity to enable tumor cell killing after energy pathways such as glucose and mitochondrial metabolism were increased. During these studies we found T cells in the blood of the same patients that showed similar exhausted characteristics and altered metabolism. Because blood T cells are readily accessible and may provide a marker for antitumor immunity, we next examined blood of kidney cancer patients receiving standard of care immune therapy treatments for changes to T cell populations. Preliminary data suggests T cells subsets defined by metabolic and exhausted characteristics changed during treatment and may correlate to a patient s response on therapy. This proposal seeks to understand if measuring the metabolic characteristics of T cells in the peripheral blood of patients can reflect tumor experienced T cells and may serve as noninvasive method to correlate with how a patient may respond to immune therapy. The work proposed in this grant will touch upon multiple KCRP Focus areas including (1) conducting basic biologic research to further our understanding of kidney cancer, (2) to identify and develop novel methods to understand and predict response to treatment with biomarkers. The proposed work to understand peripheral blood immune metabolism as it relates to the tumor immune microenvironment and response to immune therapy may lead to a noninvasive liquid biopsy that would serve as a reflection of a patient s tumor and correlate to response seen in immune based therapy. While the focus of this work is on patients with clear cell type kidney cancer, it is possible that understanding immune cell changes in the peripheral blood will be more broadly applicable across different histologic types of cancer. We believe these experiments could be directly translatable into clinical trials for prospective validation of findings with a goal of informing patient care in the short term. This grant application has several innovative approaches including use of immune metabolism as a reflection of the tumor immune microenvironment and use of liquid biopsy capturing response to systemic immune therapy.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310921
Entities
People
- Kathryn Beckermann
Organizations
- United States Army
- Vanderbilt University