Ricerc@Sapienza

Increasing evidence strongly suggests that bevacizumab compound impacts the
immunological signature of cancer patients and normalizes tumor vasculature. This study aims to
investigate the correlation between the clinical response to bevacizumab-based chemotherapy and
the improvement of immune fitness of multi-treated ovarian cancer patients. Peripheral blood
mononuclear cells (PBMCs) of 20 consecutive recurrent ovarian cancer patients retrospectively
selected to have received bevacizumab or non-bevacizumab-based chemotherapy (Bev group and
Ctrl group, respectively) were analyzed. CD4, CD8, and regulatory T cell (Treg) subsets were
monitored at the beginning (T0) and after three and six cycles of treatment, together with IL10
production. A lower activated and resting Treg subset was found in the Bev group compared with
the Ctrl group until the third therapy cycle, suggesting a reduced immunosuppressive signature.
Indeed, clinically responding patients in the Bev group showed a high percentage of nonsuppressive
Treg and a significant lower IL10 production compared with non-responding patients
in the Bev group after three cycles. Furthermore, clinically responding patients showed a discrete
population of effector T cell at T0 independent of the therapeutic regimen. This subset was
maintained throughout the therapy in only the Bev group. This study evidences that bevacizumab
could affect the clinical response of cancer patients, reducing the percentage of Treg and sustaining
the circulation of the effector T cells. Results also provide a first rationale regarding the positive
immunologic synergism of combining bevacizumab with immunotherapy in multi-treated ovarian
cancer patients.