Radiation induces iatrogenic immunosuppression by indirectly affecting hematopoiesis in bone marrow

Area of Science:

• Immunology
• Cancer Therapy
• Radiation Oncology

Background:

• Immunotherapy is revolutionizing cancer treatment.
• Radiation therapy can cause immunosuppression, known as radiation-induced lymphopenia (RIL).
• RIL is linked to poorer patient survival, but its mechanisms remain unclear.

Purpose of the Study:

• To investigate the underlying mechanisms of radiation-induced lymphopenia (RIL).
• To understand how radiation affects immune cells and bone marrow.

Main Methods:

• Irradiation effects on circulating lymphocytes, spleen, thymus, and bone marrow were analyzed.
• Mass cytometry (CyTOF) was used to analyze bone marrow cell expression.
• RNA Sequencing and gene set enrichment analysis were performed on bone marrow cells.

Main Results:

• Irradiation caused indirect effects on lymphoid organs, including the bone marrow.
• Irradiated cells trafficked to the bone marrow, reducing hematopoietic stem cells (HSC) and progenitor cells.
• Reduced CD11a expression and down-regulation of hematopoiesis-related genes were observed in bone marrow post-irradiation.

Conclusions:

• Radiation therapy impacts not only circulating lymphocytes but also bone marrow function.
• Mechanisms of RIL involve reduced HSCs, impaired T cell maturation (CD11a reduction), and altered hematopoiesis.
• Identifying these mechanisms can inform strategies to mitigate RIL in cancer patients.