Discovering Novel Methods for Linking CD8 Imaging and Outcomes in Melanoma

Why This Research Matters
Immunotherapy, which activates the patient’s own immune system to recognize and attack cancer cells, is one of the most effective treatments for melanoma. Neoadjuvant immunotherapy is given before planned surgical removal of a tumor. The standard way to tell if treatment is working is that tumors shrink on CT scans, but successful neoadjuvant immunotherapy may help patients without producing much change in tumor size. This study explores a new method of analyzing non-invasive imaging that may enable better detection of whether the immune system is successfully attacking the tumor in neoadjuvant treatment.  

What We Are Studying
T cells are part of the immune system that identify and kill cancer cells. Research shows that a high number of CD8 T cells inside a tumor is one of the strongest signs that immunotherapy will succeed. The most direct way to measure T cells is to stain tumors to see if they have CD8 and examine them under a microscope. This requires a sample from surgical removal of the tumor or a needle biopsy. Both are too invasive to be repeated often, plus a needle biopsy samples only a small part of a tumor and may therefore miss areas containing many CD8 T cells. Our prior research showed that CD8 PET scans, which use a radioactive tracer that binds to CD8 T cells, can safely and non-invasively visualize CD8 throughout the tumor. However, the estimate of CD8 cells using PET was not well-matched to the count from a needle biopsy. In other studies, we have found that a newer computer-based method of analyzing imaging data called radiomics can estimate tumor CD8 levels on CT scans. This study tests whether radiomics analysis of CD8 PET and CT scans can improve the prediction of CD8 levels and neoadjuvant treatment success.

How the Study Works
Because 20 of these patients had CD8 PET scans before immunotherapy and before surgery, and all 28 patients had CT scans, we can study how well the imaging estimates of CD8 on PET or CT matched the count of stained cells in the surgical sample. About half of the patients showed a major pathologic response when their tumors were examined after surgery, allowing us to also test whether imaging measurements of CD8 can identify patients whose tumors responded to immunotherapy.

Expected Impact
This study is an important step toward developing imaging biomarkers that could ultimately help doctors identify effective or ineffective treatments earlier, reduce unnecessary treatment and toxicity, and accelerate the development of new cancer therapies. The project will also provide a junior melanoma researcher with training in radiomic imaging analysis and support the development of larger future studies.