SWOG Cancer Research Network Study Opens Window on Immune Microenvironment

The First Comprehensive Study of Types of Immune Cells in Cancer Tissues Before and After Chemotherapy Highlights Multiple Targets for New or Existing Cancer Drugs that Could Improve Patients' Sensitivity to Chemotherapy and Immunotherapy .

The results of the SWOG Cancer Research Network study appear in the latest issue of Journal of Cancer Immunotherapy. The results provide a detailed overview of the immune cells present in bad cancer tumors before and after chemotherapy, providing scientists with a rare window into the immune microenvironment and the effects it has on anticancer drugs.

"When we better understand the types and functions of immune cells in cancer tissue and the effects of drugs on these cells, we will come closer to finding effective treatments," said Lajos Pusztai, MD, Chair of the Cancer Committee. SWOG bad and senior. author of the newspaper article. "Through this study, we gain a unique insight into the immune microenvironment of the tumor and identify potential therapeutic targets that can be clinically tested."

SWOG is a public cancer research network that has conducted more than 1,400 trials funded by the National Cancer Institute since 1956. A major benefit of this longevity: the accumulation of more than 800,000 blood samples, tissue and others in the SWOG Biobank. Pusztai, from the Yale Cancer Treatment Center, and his SWOG team located 60 paired tissue samples from the bank, which were collected for S0800, a randomized trial comparing two pre-surgical chemotherapy treatments for patients with 39, HER2 negative, locally advanced or inflammatory bad cancer.

The team used this subset of matched tissues before and after treatment to achieve three goals: to determine the presence of cancer-fighting immune cells known as tumor infiltrating lymphocytes (TILs); measure the expression of the PD-L1 immune inhibitory protein, as well as the expression of 750 other genes related to the immune system that can show the activity of immune cells in the tissues before and after treatment.

To do this work, Pusztai and his team used three methods. These included a pathologist who counted TILs under the microscope and laboratory scientists using a test to determine PD-L1 expression. In addition, the main author of the article, Xiaotong Li, computer scientist biologist at Yale, used another test, the NanoString gene expression group PanCancer IO 360, to measure expression of 750 genes related to the immune system with the help of a NanoString team.

Here are the results:

• The team found more anti-cancer TIL in pretreatment tissue samples taken from patients who saw their cancer disappear after chemotherapy, a phenomenon known as complete pathological response, or pCR. The number of TIL in post-treatment tissues was significantly lower compared to pre-treatment tissues, suggesting that immune cells are destroyed by chemotherapy agents.
• The researchers found no significant changes in the expression of PD-L1 protein in any of the comparator groups – between patients whose tumors disappeared and those whose tumors simply narrowed, or between tissue samples before and after treatment.
• The team discovered 24 more strongly expressed immune genes in patients who had a complete response to chemotherapy, including genes that control the killer enzymes of granzyme and granulysin cells and the cytokines CCL21 and CCL19, cell-activating proteins. T fight against cancer. The IL7R gene that controls the production of T-calls is also more active in patients who have seen their cancer disappear after chemotherapy. This suggests that these molecules play an important role in the activation and attraction of immune cells – and that any drug that increases their expression or activity could improve the response to treatment.
• The team found that the CXCL1, CXCL2, CXCL3 and CCL20 proteins, as well as the IL6 gene, were more expressed in patients who did not achieve a complete response to chemotherapy. This suggests that drugs that decrease the presence of these proteins and the activity of this gene could improve the response to treatment.

"Our results revealed several highly effective immune targets that can be clinically tested," said Pusztai. And, in fact, he's already doing it. Pusztai directs S1418, a bad cancer trial of SWOG, which tests pembrolizumab immunotherapy, which targets PD-1, to determine whether it will improve the survival of patients with cancer triple negative bad after preoperative chemotherapy. .

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