Analyzing tumors of cancer patients with robust response to treatment may offer clues on how others can benefit and improve tailored treatment

Patients who have a better-than-average response to cancer treatment can help further research that might benefit all cancer patients. Analysis of their tumor tissues can provide clues about the genetic keys that make their tumor more responsive to treatment.  

 

Elijah Edmondson used slide scanners and cell detection algorithms, digital pathology tools to quantify the number of cancer cells per square millimeter.
Fig 1. Tumor tissue from a patient with Uterine Corpus Endometrial Carcinoma (UCEC) was fixed in formalin and routinely processed for pathology evaluation.
The above images are taken from a 5um thick section of tumor tissue stained using immunohistochemistry to identify CD8+ Tumor Infiltrating Lymphocytes.
The higher power image demonstrates positive cells (brown) infiltrating the tumor.

 

Researchers in the National Cancer Institute’s Exceptional Responders Initiative recently reported in the Journal of the National Cancer Institute that comparing the molecular makeup of an exceptional responder’s tumor before and after treatment is a valuable way to learn more about cancer, especially when comparing it to other patients who underwent the same treatment.  

This multi-institutional molecular profiling effort involved two laboratories at the Frederick National Laboratory for Cancer Research, which performed tumor analysis for the study and as part of follow-on research for the exceptional responder projects. Elijah Edmondson, DVM, PhD, with the Molecular Histopathology Laboratory and Chris Karlovich, PhD, with the Molecular Characterization Laboratory are authors on the paper. 

Exceptional responders are those who had a complete response or a long-lasting partial response to a treatment to which fewer than 10 percent of patients experienced the same. They also must sustain a complete or partial response to the treatment for at least three times longer than the median duration of response found in the scientific literature for that treatment. 

 

Elijah Edmondson used slide scanners and cell detection algorithms, digital pathology tools to quantify the number of cancer cells per square millimeter.
Fig 2. Whole slides images were created (top image) using slide scanners
and cell detection algorithms were generated
to quantify the number of positive cells per mm^2;
a pseudocolor image mask (bottom) identifies positive cells as red. 

 

Edmondson quantified tumor-infiltrating lymphocytes, immune cells that can recognize and kill cancer cells, using immunohistochemistry and digital pathology methods to characterize how well the patient’s immune system responded to the cancer. The “adaptive immune response” to a tumor can vary between patients and can be estimated using immunohistochemistry to stain tumor biopsy tissue for specific immune cell populations, such as CD8 T-cells. After staining the CD8 cells on the slide, Edmondson took whole slide images of the tumor to obtain a quantitative measure of the cells infiltrating the tumor. 

“Digital pathology paints a picture of the immune surveillance in cancer, which may suggest why these patients did well on treatment,” he said.  

The molecular pathology and image analysis is one part of this larger study and the data was evaluated in the context of other types of data analyzed for exceptional responder patients, Edmondson added, including whole exome sequencing, deep-target sequencing, DNA methylation, RNA-seq, and a NanoString immune oncology gene expression profiling panel. 

“The pilot study for evaluating exceptional responses to treatment is hopefully just the beginning of efforts to better understand the molecular responses underlying these exceptional responders,” Edmondson said. “These efforts are moving forward with a goal of improving the molecular understanding of exceptional cancer responses and additional findings are currently under peer review.” 

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