Abstract: Gynecologic Oncology has changed in the last few decades. An increasing proportion of patients is benefiting from long term survival although patients diagnosed with advanced disease suffer from a poor prognosis. Unfortunately, several recent studies are confirming that changing the combinations of "traditional" cytotoxic drugs is unlikely to obtain a real breakthrough in survival rates. Furthermore, there is discouraging data regarding consolidation therapies. It is, therefore, necessary to identify new target therapies with a minimal impact on quality of life. It is likely that new breakthroughs are only going to be achieved when changes in therapies are tailored to the entire natural history of the disease and on specific patient characteristic's. Since the discovery that tumor infiltrating lymphocytes represent an independent prognostic factor in ovarian cancer patients, several researchers have dedicated their attention to cancer immune response in order to identify prognostic factors and immunological targets. Analyses on immunophenotype at diagnosis and throughout the entire course of treatment are currently ongoing and are giving the new diagnostic, prognostic and therapeutic tools to the physicians. Furthermore new antigens and new vaccination strategies are being investigated. Encouraging data on selected patient populations have been observed recently. The objective of the present review is to define the immunology of women affected by gynecological malignancies and describe new immunological targets for prognostic and therapeutic use.
Abstract: The incidence of multiple primary cancers has greatly increased in the last decade. We report the first case of a woman who suffered from 3 distinct HPV-induced neoplasms: cervical, vulvar, and head and neck carcinomas.
Abstract: Abstract Surgery is the primary therapeutic strategy for most solid tumors, despite modern oncology has established that neoplasms are frequently systemic diseases. Being however a local treatment, the mechanisms through which surgery plays its systemic role remain unknown. We have investigated the influence of cytoreduction on the immune system of primary and recurrent ovarian cancer. All ovarian cancer patients show an increase in CD4(+)CD25(+)FOXP3(+) circulating cells (CD4 T(reg)). CD4/CD8 ratio is increased in primary tumors but not in recurrent neoplasms. Primary cytoreduction is able to increase circulating CD4 and CD8 effector cells and decrease CD4 naïve T cells. CD4(+) T(reg) cells rapidly decreased after primary tumor debulking, while CD8(+)CD25(+)FOXP3(+) (CD8 T(reg)) cells are not detectable in peripheral blood. Similar results on CD4 T(reg) were observed with chemical debulking in women subjected to neoadjuvant chemotherapy. CD4 and CD8 T(reg) cells are both present in neoplastic tissue. IL-10 serum levels decrease after surgery, while no changes are observed in TGF-beta1 and IL-6 levels. Surgically induced reduction of the immunosuppressive environment results in an increased capacity of CD8(+) T cells to respond to the recall antigens. None of these changes was observed in patients previously subjected to chemotherapy or affected by recurrent disease. In conclusion, we demonstrate in ovarian cancer that primary debulking is associated with a reduction of circulating T(reg) and an increase in CD8 T cell function. Debulking plays a beneficial systemic effect by reverting immunosuppression and restoring immunological fitness.
