The immune checkpoint receptor TIM-3 could be a promising path toward treating pleural mesothelioma, a Belgium study suggests.
The research, “Prognostic and predictive aspects of the tumor immune microenvironment and immune checkpoints in malignant pleural mesothelioma,” was published in the medical journal OncoImmunology.
Immune checkpoint proteins are molecules found on the surface of certain immune cells, such as T-cells, to keep the immune system in check, or stop it from overreacting. However, the molecules can also keep immune cells from killing cancer cells. So blocking immune checkpoint proteins could help the immune system destroy cancer cells.
Previous research has shown that the immune system can protect against malignant pleural mesothelioma (MPM), a rare and aggressive type of cancer. Shedding light on the tumor immune micro-environment — that is, the immune molecules that surround tumor cells — and the immune checkpoint molecules that tumor cells express could identify new immune-based cancer therapy possibilities.
A team of researchers led by Dr. Evelien Smits of the University of Antwerp used a technique called immunohistochemistry to look at molecules expressed in the lung tissues of 54 MPM patients. Forty samples were collected at the time of diagnosis and 14 after chemotherapy.
The researchers examined 10 molecules that are known to be involved in the tumor immune micro-environment and immune checkpoint system. They were PD-1, PD-L1, TIM-3, LAG-3, CD4, CD8, CD45RO, granzyme B, FoxP3, and CD68.
They found that three molecules, TIM-3, PD-1, and PD-L1, were expressed on the surface of both immune cells and tumor cells.
Interestingly, PD-1 and PD-L1 were expressed only on tumor cells taken from patients who had received chemotherapy. The researchers concluded that chemotherapy changes the expression of immune checkpoint molecules. This suggested that it is important for doctors to carefully plan treatment schedules for combinations of chemotherapy and immune therapy.
Researchers also found that CD45RO expression was a negative predictive factor for response to chemotherapy. In other words, patients with high levels of CD45RO-positive tumor immune cells were less likely to respond to chemotherapy. Conversely, the expression of CD4 and TIM-3 in clusters of immune cells were predictors of better disease outcome.
The team concluded that the tumor immune micro-environment could predict whether or not a patient will respond to chemotherapy. They also suggested that TIM-3 could be a promising new target in mesothelioma. More research is needed to confirm the potential therapeutic benefits of targeting the receptor, they said.
MPM develops in the thin layer of tissue surrounding the lungs called the pleura. The incidence of this cancer is on the rise. More than 2,000 people are diagnosed each year in the United States, underscoring the urgency to develop new therapeutic strategies.
