Predicting Which Cells Can Take The BiTE Out Of Cancer

Using bispecific T-cell engager technology, or BiTE, researchers in Japan have found that the cancer-killing activity of T-cells in tumors can be estimated from T-cells in the blood.

AsianScientist (Mar. 7, 2019) – A team of scientists in Japan has found a way to identify lung cancer patients who would benefit from cancer immunotherapy, based on the activity of the patients’ immune cells in the blood. Their findings are published in the journal Scientific Reports.

Immune cells called T-cells are key players in the fight against cancer. However, T-cells sometimes struggle to recognize cancerous cells or fail to launch an appropriate response against them. T-cell activities can be tweaked to improve their anticancer effects using cancer immunotherapy, but this is only effective for a subset of patients, who are difficult to identify in advance.

In the present study, researchers led by Professor Atsushi Kumanogoh at Osaka University, Japan, have found a way to measure cancer cell-killing activity of T-cells in tumors of lung cancer patients by examining the activity of T-cells in the blood. They used an approach called bispecific T-cell engager technology (BiTE), which ensures that T-cells encounter cancer cells, to assess the intensity of anticancer activity in these immune cells.

The team first compared the cell-killing activity of T-cells from lung cancer tumors, healthy lung tissue and peripheral blood. At the same time, the cell-killing activity of patients’ T-cells was correlated with factors such as whether the patient was a smoker, the presence of certain gene mutations and the levels of immunity-related molecules called cytokines.

“After optimizing the BiTE conditions for assaying T-cell cytotoxicity, we characterized the T-cells from the three sample sets and looked at their correlations with other clinical and lifestyle-related factors,” said Kumanogoh. “We first found that T-cells were more cytotoxic in smokers and that high T-cell cytotoxicity within tumors was linked to the expression of some cytokines.”

The researchers further showed that the cytotoxicity of T-cells in the blood most strongly predicted the cytotoxicity of T-cells within lung tumors. The cancer cell-killing activity of T-cells also reflected the effectiveness of the immune checkpoint inhibitor nivolumab at destroying tumor cells.

“The ability to diagnose cases using just blood samples would mean that patients won’t have to undergo invasive procedures such as biopsy for tumors in the lungs,” said Dr. Kota Iwahori who is the first author of the study. “We could then evaluate whether the use of cancer immunotherapy would be appropriate for a particular patient, hopefully improving the outcomes in lung cancer patients.”

The article can be found at: Iwahori et al. (2019) Peripheral T-Cell Cytotoxicity Predicts T-Cell Function in the Tumor Microenvironment.


Source: Osaka University; Photo: Shutterstock.
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