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Recently, the combining of different drugs has greatly improved response and survival rates in gynecological malignancies. Results are however far from being satisfactory. Treatments used in case of advanced or recurrent disease offer limited results in terms of long-term responses. The urgent need for new and more effective treatments has prompted researchers to investigate and propose new therapeutic strategies. One of the most interesting approaches that are being explored is constituted by immunotherapy. Currently, immunotherapeutic strategies include vaccination with peptide, viral vectors, carbohydrates and antiidiotypic antibodies. In addition, cell based immunotherapy has been adopted in vitro activated lymphocytes and dendritic cells. Most experience has been acquired in ovarian cancer and cervical cancer. Little has been investigated in endometrial and rare gynecologic neoplasms. The clinical experiences and results achieved with immunotherapy in this setting of patients have been reviewed and the future avenues that are currently being explored have also been discussed.

Dendritic cells (DCs) are able to orchestrate innate and acquired immunity and can activate and sustain a long-lasting anti-tumor immune response in vivowhen used as anti-tumor cell therapy. The selection of the antigen and the choice of its formulation are key points in designing anti-cancer DC-based vaccines. Cell released vesicles/exosomes have been shown to transfer antigens, HLAI/peptide complexes and co-stimulatory molecules to recipient cells. In this study we describe the generation of an allogenic microvesicle cell factory in which the expression of a specific tumor antigen was combined to the expression of co-stimulatory and allogeneic molecules. The DG75 lymphoblastoid cell line was selected as microvesicle producer and transfected with ErbB2, as tumor antigen prototype. The shed microvesicles transferred antigenic components to recipient DCs, increasing their immunogenicity. DC pulsing resulted in cross-presentation of ErbB2 both in HLAI and HLAII compartments, and ErbB2-specific CD8+T cells from cancer patients were activated by DCs pulsed with vesicle-bound ErbB2. The microvesicle cell factory proposed may represent a source of cell free immunogen to be used for DC-based cancer therapy.

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 characteristics. 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.