New analysis explains why bone marrow cancer T cells may need therapeutic activation

Researchers from the German Cancer Research Center, the HI-STEM Stem Cell Institute, and Medical Clinic V at Heidelberg University Hospital have conducted a comprehensive study on T cells in the bone marrow of patients with multiple myeloma and acute myeloid leukemia. Their findings, published in Cancer Cell, reveal that certain tumor-reactive T cells in the bone marrow differ significantly from those in solid tumors.

These bone marrow T cells are capable of recognizing and potentially fighting cancer cells but remain in a state of conditional preparedness, rather than being chronically exhausted. Although they possess the necessary biological tools, they are not activated sufficiently or continuously within the body. This could explain why some immunotherapies have varying degrees of effectiveness against blood and bone marrow cancers.

The researchers identified a specific 15-gene signature that can distinguish these tumor-reactive T cells from other immune cells. This signature achieved high predictive accuracy in an independent group of patients, suggesting its potential as a tool to predict the success of immunotherapies. Higher baseline levels of these cells were associated with a more favorable clinical course in multiple myeloma and acute myeloid leukemia.

However, the study also found that these signature cells did not predict the success of conventional chemotherapy, indicating that the signature reflects the immune system's activity rather than the general disease course. The researchers also identified common tumor antigens recognized by these T cells, which could potentially support the development of more broadly applicable immunotherapies in the future.