CD8 T-Cell Infiltration as a Predictor of Renal Cancer Progression After Surgery
Abstract
Scientific Objective and Rationale: In 2019, patients and caregivers who faced a diagnosis of a large non-metastatic kidney cancer are given a recommendation for surgery. Almost all want to know the answer to the following question, "After this surgery, how am I going to do?" Further, many patients who have a diagnosis of a "bad" kidney cancer want to know why it is a bad kidney cancer (and can something be done about it). Current methods of prognostication are based, in large part, on traditional pathology variables and assessment of patient performance status. This Translational Research Partnership grant application is written by a surgeon-scientist (Viraj Master, M.D. Ph.D.) and an immunologist (Haydn Kissick, Ph.D.). For over a decade, Dr. Master has had clinical and scientific focus on kidney cancer. Some patients with very advanced kidney tumors were cured and lived without other treatment, while others died after developing metastatic disease, sometimes remarkably quickly, even though they had the same pathology features. It is not easy to identify which patient was in which group. The answers to understanding which patient will be cured, and which patient is not cured and needs a trial or adjuvant therapy, is of utmost importance. Since 2007, to try and answer this question, moving beyond traditional risk assessment (pathology) measurements, Dr. Master has been interested in understanding the role of the serum markers of immunity/inflammation that could inform patients about how they would do after surgery, and after systemic therapy as well. Working collaboratively, his team found robust, widely available serum markers, both pre- and post-operatively, that would be helpful in prognosticating outcome, in literally hundreds of patients, that have been validated outside of Emory, including internationally. In the past 4 years, since he and Dr. Kissick started working together, they started to use advanced immunological techniques to answer this question. They found there can be as much as a 10,000-fold difference in the amount of T cells in kidney tumor between patients. Preliminary data from 171 patients has shown those patients with a low amount of CD8 T cells in kidney cancers, of any histology, will progress to metastatic disease, while those with a higher CD8 T cell count will not. In this grant, the first aim is to develop and validate an assay that can easily measure the %CD8 count in patient tumors from any normal pathology work-flow by studying patients from Emory Hospital, Grady Hospital (an inner city hospital), as well as from the Atlanta VA hospital, recruiting Veterans. A validation cohort will come from a close collaborator at the University of Wisconsin. A highly exploratory sub-aim is to investigate whether the %CD8 T cells in the initial resection specimen can determine treatment success with systemic therapies if relapse occurs. The second aim is to understand the mechanism that allows for some patients to have a robust CD8 response, while other patients have a virtual absence of T cells. Preliminary research in the lab has shown that clusters of antigen-presenting cells localize with stem-like T cells in patients with a robust amount of "killer" T cells. We seek to understand how these clusters come together. Once the mechanism is understood, future rational clinical trials can be designed to foster development of these niches. Applicability Patient types: This research will help both patients with the most common form of kidney cancer, clear cell renal cell carcinoma, as well as those patients with non-clear histologies, of which the latter group has not been studied as much as ccRCC patients. Since one of the PIs also performs operations at a safety net hospital, a significant fraction of minority patients are in our cohort, and will continue to be accrued. Clinical Applications/Benefits/Risks: We will augment the traditional prognostic tools available to kidney
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010526
Entities
People
- Viraj A Master
Organizations
- Emory University
- United States Army