A team of researchers at Roswell Park Comprehensive Cancer Center has identified a new biomarker that may predict a response to immune checkers (ICI) shortly after patients with non-small cell lung cancer ( NSCLC) start treatment. This discovery, published today in the journal Nature Communication, is not only an important step forward in the treatment of lung cancer, but it also affects other malignancies, according to lead author Fumito Ito, MD, PhD, FACS.
Although ICI changed the treatment of cancer for large numbers of people, many cancer patients do not respond to them, and some develop severe toxicity. ”
Dr. Fumito Ito, Associate Professor of Medical and Ball Oncology, Immunotherapy Center, Roswell Park
Pretreatment biomarkers such as PD-L1 expression, frequency of tumor-infiltrating lymphocytes and tumor mutational burden have limited value in guiding decisions about which patients are more likely to respond well to checkers. Tumor biopsy shortly after the start of ICI therapy can provide useful information, but it is invasive and difficult to perform in patients with cancer of the visceral organ, or internally -; such as lung cancer.
The detection of blood-based biomarkers that mimic the micro-environment change of the tumor and may predict patient response to ICIs could significantly improve the mechanisms routine treatment, Dr. Ito notes. Previous work from this group shows that T cells with different levels of the chemokine receptor CX3CR1 responded in a different way to immunotherapy with check inhibitors.
Building on these findings, the researchers attempted to validate the utility of that protein, CX3CR1, as a T-cell biomarker for ICI therapy. They found that effective checkpoint inhibitory therapy is associated with increased frequency and clonality of some CX3CR1-positive T cells; that the frequency of these CD8 + T cells was increased during ICI treatment; and that there is considerable genomic similarity between CD8 + tumor-infiltrating lymphocytes (TILs) and this subset of CX3CR1-positive T cells.
To confirm this in patients, the researchers obtained serial blood samples from patients with NSCLC receiving anti-PD-1 treatment. The team, which also included two Roswell Park medical oncologists, Grace Dy, MD, Head of Thoracic Oncology, and Hongbin Chen, MD, PhD, Associate Professor of Oncology, saw changes in CX3CR1 frequency in blood associated with response to ICI therapy.
Dr. Ito and colleagues cited a percentage change of the CX3CR1-positive subset in CD8 + T blood cells from baseline as a “CX3CR1 score,” and found that a CX3CR1 score of at least 20 was true. correct in predicting the response and prognosis of NSCLC patients receiving anti-PD-1 treatment.
“Right now, we need a better biomarker to predict the response to immunotherapy, which is part of routine treatment in advanced and metastatic lung cancer,” says Dr. Chen. “This study sheds light on a promising blood-based biomarker that may be very useful in identifying which patients with lung cancer are most likely to benefit from immunotherapy. We are looking at continue to explore its usefulness in further clinical study. “
The team is designing clinical studies to further investigate the potential usefulness of this biomarker in guiding treatment decisions for cancer patients.
Source:
Roswell Park Comprehensive Cancer Center
Magazine Reference:
Yamauchi, T.,. et al. (2021) CX3CR1 T-cell expression as a blood-based dynamic biomarker in response to immune checkers. Nature Communication. doi.org/10.1038/s41467-021-21619-0.