Single-cell evaluation illuminates the myeloma immune landscape

Scientists on the Icahn School of Medicine at Mount Sinai, in collaboration with the Multiple Myeloma Research Foundation (MMRF) and in collaboration with leading institutions across the country, have helped create the most important single-cell immune cell atlas of the bone marrow in patients with multiple myeloma, a blood cancer that’s treatable but still incurable. The outcomes published in provide unprecedented insights into immune deficiency in myeloma and may lead to improved tools for predicting which patients are at higher risk of relapse after treatment.

The study analyzed nearly 1.5 million immune cells from the bone marrow of 335 newly diagnosed patients within the MMRF’s CoMMpass study data set, using a cutting-edge technique called single-cell RNA sequencing. This approach allowed researchers to look at the molecular characteristics of individual cells and uncover previously hidden patterns within the behavior of the immune system within the presence of multiple myeloma.

Currently, doctors rely heavily on the genetic characteristics of cancer cells to estimate how aggressive their disease is. Our research shows that the immune cells surrounding the tumor are equally necessary in disease progression, and this may lead to earlier, more targeted treatment strategies.”

Sacha Gnjatic, PhD, co-senior writer, professor of immunology and ImmunotherapyMount Sinai Tisch Cancer Center

“The dimensions and maturity of the MMRF’s CoMMpass study and the breadth of this multicenter collaboration underscore the importance of forming ‘big science teams,'” added George Mulligan, PhD, co-senior writer and chief scientific officer of the MMRF.

The team discovered that some patients who relapsed quickly after initial therapy had distinct immune cell populations within the bone marrow on the time of diagnosis. Particularly, a subset of T cells (immune cells typically liable for attacking tumors) appeared to indicate a state of immunosenescence, meaning they were present but not functioning effectively, contributing to immunosuppression. As well as, the study uncovered communication patterns between immune cells and cancer cells that might support tumor growth.

These findings suggest that the immune system’s response to myeloma might be used as a predictive tool and complement traditional genetic testing. While the technology currently utilized in the study is primarily for research, the researchers hope that the outcomes will inform the event of easy, widely available tests in the longer term.

“This work not only provides recent biological insights, but additionally lays the inspiration for future discoveries,” said Dr. Gnjatic. “It could help researchers world wide higher understand how the immune system interacts with cancer and ultimately help improve outcomes for patients.”

The MMRF designed and funded this collaborative research, which included equal contributions from scientists at Mount Sinai, Emory University, Beth Israel Deaconess Medical Center, Washington University Siteman Cancer Center in St. Louis, Mayo Clinic, and MMRF. Edgar Gonzalez-Kozlova, PhD of Mount Sinai, was co-first writer together with other senior data analysts from the six institutions. Other key Mount Sinai contributors included Seunghee Kim-Schulze, PhD, data generation lead, and Hearn J. Cho, MD/PhD, a Mount Sinai myeloma oncologist and researcher who can also be chief medical officer at MMRF.

The massive patient sample size and robust clinical annotations – made possible by the MMRF’s extensive biorepository and 12 years of patient data – make this resource probably the most comprehensive resources of its kind. This report will contribute significantly to our understanding of immune function in multiple myeloma.