CANCER THERAPY INDUCED DISRUPTION OF B CELL MEMORY IN THE BONE MARROW STROMAL NICHE AND SECONDARY LYMPHOID TISSUE; IMPLICATIONS FOR VACCINE RESPONSES

Aims Assess the mechanisms causing loss of B cell memory after cancer therapy.Background Re-vaccination after cancer does not always re-establish protective antibody(Ab)titers.

We hypothesize that Ab-producing cells show mitigated responses to activation, trafficking and survival signals provided by stromal cells (SCs) in lymphoid tissue (SLTs).Preliminary results In our  animal model, memory B cells (MBCs) in the bone marrow and blood are eradicated by chemotherapy but recover after a few weeks, while vaccine-specific IgG recall responses by MBCs in SLTs are still impaired six months after chemotherapy.

In SCs, chemotherapy alters the gene expression profile and protein secretion of factors important for ab-producing cells.Workplan & methods I will  i) evaluate the ability of MBC post chemotherapy to proliferate and differentiate to ab-producing cells upon different stimuli using flow cytometry, Elispot, proteome profiling and RNA seq ii) study the SCs and the relation to MBCs in SLTs by confocal microscopy in longitudinal samples from our animal model and describe the pattern of systemic mediators connected to function, maintenance and homing of MBCs during the course of cancer treatment by proteome profiling iii) assess an array of serum proteins connected to MBC- and Ab-responses in children with cancer Significance Protecting cancer patients from infections will improve overall survival and re-immunisation is important to reduce late infectious complications.