Researchers from Mayo Clinic have uncovered understanding of how lung tumors weaken the immune system. The finding may help explain why some lung cancer patients fail to respond to immunotherapy, and it could lay groundwork for a modified therapeutic approach that increases efficacy.
The research findings were published in the paper, “Regulatory T-Cell Sensing of Extracellular ATP via P2RX7 Promotes Their Accumulation and Suppression and Drives Lung Tumor Growth,” in Cancer Immunology Research.
In the study, Mayo researchers and collaborators analyzed data from patients who had nonsmall cell lung cancer. Their focus was the behavior of regulatory T cells, which under normal circumstances maintain a person’s immune system, but in people with lung cancer, these cells redirect to protect the tumor instead of the whole body.
“What we are seeing is the tumor taking advantage of a normal immune safety mechanism and turning it to its own benefit,” said senior author Henrique Borges da Silva, PhD, an immunologist at Mayo Clinic in Arizona, in a news release.
This role reversal can impact the success of immunotherapy by impairing immune cell function and allowing lung tumors to grow.
According to the researchers, regulatory T cells located inside lung tumors showed high levels of P2RX7 — an immune cell receptor that senses stress or danger and controls inflammatory responses. Increased P2RX7 impacted the ability to detect ATP, thereby diminishing survival outcomes.
The group found that removing P2RX7 from regulatory T cells caused lung tumors to slow growth because the immune system was less suppressed, allowing the cancer-fighting cells to concentrate in the tumors and hinder immune activity.
Another benefit to blocking P2RX7, researchers found, is it allowed immune cells to operate more closely with B cells, which caused an upsurge of tumor-targeting antibodies. The more immune cells can group together inside a tumor, the better the response to cancer treatment, the researchers said.
“If we want immunotherapy to reach more patients, we have to understand why it fails,” Dr. Borges da Silva said. “This study identifies one of the mechanisms standing in the way.”
As part of the study, researchers administered a drug that inhibits P2RX7 in models and determined it developed smaller lung tumors with less concentrated regulatory T cells inside the tumors. The drug is not approved for cancer treatment, but the researchers said it could be an important addition to existing immunotherapies.
Overall, the authors said the study demonstrated the role targeted immune suppressants can have on lung cancer tumor therapies; however, additional research is needed prior to clinical trials in patients.
