A team led by Daniel Peeper (NKI, Oncode Institute) co-cultured melanoma cells with T cells to study their interactions. “We observed that T cells that specifically recognize tumor cells stick to them very tightly to form clusters,” says Sofía Ibáñez-Molero, co–first author of the study. “These T cells were much more effective at killing cancer cells than individual, unbound T cells.”
This result led the researchers to a new idea: could this be a way to identify and select the tumor-killing T cells from tumors directly? The breakthrough came when the team showed that the interactions between active T cells and cancer cells are so strong that these clusters can indeed be isolated straight from a patient’s tumor. Using this approach, they could identify the active, tumor-recognizing T cells faster and more easily than with existing methods. In the lab and in mice carrying patient-derived tumors, these T cells were up to nine times more effective at destroying cancer cells.
Until now, cancer studies have focused mostly on individual T cells. “Those analyses have yielded valuable insights. But our study shows that we can also learn a lot from T cells that form clusters with tumor cells. What’s also special about these clusters is that they carry features that may help predict whether a patient will respond well to immunotherapy,” adds Johanna Veldman, senior postdoc and co–first author.
“It actually makes sense that active T cells need to firmly attach to cancer cells before they can kill them,” says Peeper. “Yet we’ve long overlooked that this property could be used to obtain the T cells that are highly active against cancer. “By purifying these active T-cell clusters from tumors, we may be able to improve current TIL therapy.”