Dr McCarthy on Neutrophil Activity in Multiple Myeloma

Philip McCarthy, MD, director emeritus, Transplant & Cellular Therapy Program, member, Tumor Immunology and Immunotherapy Program, Roswell Park Comprehensive Cancer Center, discusses findings from a study investigating neutrophil gene signatures within focal lesions that are linked to progression-free survival in patients with multiple myeloma.

Multiple myeloma can present diffusely in bone marrow or focally through osteolytic and extramedullary lesions, and neutrophils can comprise over half of normal bone marrow cells. Neutrophils can be altered by cancer but are understudied in multiple myeloma. However, understanding neutrophil populations in the multiple myeloma tumor microenvironment may aid the development of novel therapies for patients with this disease.

In this study, investigators observed the expression of CXCL2 and CXCL1 on neutrophils, alongside elevated levels of interleukin 8 (IL-8), all of which are integral to neutrophil chemotaxis and development, McCarthy begins. Additionally, several other cytokines and surface markers that are typically absent in healthy donor bone marrow were identified, he says. Among the inflammatory markers, IL-6 was notably upregulated, which was expected; however, investigators also found an increase in IL-10, which is known for its anti-inflammatory properties, according to McCarthy.

These findings indicate a complex interplay between malignant plasma cells within osteolytic lesions and the neutrophils that are likely drawn to these areas by chemotaxis, McCarthy explains. Although the exact role of these interactions in the development of osteolytic lesions remains unclear, it is evident that they contribute to the immunosuppressive environment that is characteristic of multiple myeloma, he notes. This immunosuppression is reflected in the hypogammaglobulinemia that is observed in many patients with multiple myeloma, which results from the suppression of normal plasma cells, McCarthy reports. Moreover, T-cell dysfunction is evident in myeloma cells, which increases the susceptibility of patients with this disease to infections that are typically controlled by T cells, such as shingles, he concludes.