Dendritic cells may play a key role in T-cell acute lymphoblastic leukemia (T-ALL), according to research published in PNAS.
Investigators identified tumor-associated dendritic cells that appeared to promote T-ALL growth and survival at primary and metastatic tumor sites in mice.
Analyses of samples from patients with T-ALL suggested dendritic cells are positioned to support T-ALL growth in humans as well.
“It’s only more recently that people have really appreciated that tumors are complex organs in and of themselves, with all of the heterogenous cell types that can talk to each other and promote each other’s survival and proliferation,” said study author Lauren Ehrlich, PhD, of the University of Texas at Austin.
Dr Ehrlich and her colleagues first found that primary T-ALL cells required tumor stroma for survival ex vivo. When T-ALL cells were cultured alone or in wild-type thymic stroma, the cells died off. Only T-ALL cells cultured with tumor-associated stroma survived.
Subsequent experiments suggested it was tumor-associated dendritic cells that spurred T-ALL growth, both for newly developing T-ALL cells and tumors that had spread to distant organs in mouse models. Tissue samples from pediatric T-ALL patients had similar growth environments with abundant dendritic cells.
To determine the mechanism by which dendritic cells support T-ALL, the investigators performed gene expression profiling. They found upregulation of PDGFRB and IGF1R on T-ALL cells, with concomitant expression of their ligands by tumor-associated dendritic cells.
The team said PDGFRB and IGF1R were activated in T-ALL cells ex vivo. And when they cocultured T-ALL cells with tumor-associated dendritic cells, they observed sustained IGF1R activation. However, they did not see this activation when they cocultured T-ALL cells with normal thymic dendritic cells.
Finally, the investigators found that IGF1R signaling was necessary for dendritic cell-mediated T-ALL survival.
The team said this is the first evidence that endogenous tumor-associated dendritic cells supply signals driving T-ALL growth.
“We hope this study will be a catalyst to spur other research groups to further elucidate the roles of dendritic cells in supporting T-ALL,” said study author Todd Triplett, PhD, also of the University of Texas at Austin.
“[T]hat could ultimately lead to the discovery of novel therapeutic targets that are more effective and less toxic than current treatment regimens.”
