Dendritic Cells Loaded with Heat Shock-Conditioned Ovarian Epithelial Carcinoma Cell Lysates Elicit T Cell-Dependent Antitumor Immune Responses In Vitro

Abstract

Ovarian epithelial carcinoma (OEC) is the most frequent ovarian tumor, characterized by a high mortality in advanced stages where conventional therapies are not effective. Based on the role of the immune system in the progression of this disease, immunotherapy using checkpoint blockade has been considered as a therapeutic alternative. Nevertheless, its results do not match up to the positive results in entities like melanoma and other malignancies, suggesting the need to find other therapies to be used alone or in combination. Dendritic cell- (DC-) based vaccines have shown promising results in several types of cancer, such as melanoma, prostate, and lung cancers, due to the essential role played by DCs in the activation of specific T cells, thus using other ways of activating the immune response than immune checkpoint blockade. During the last decade, we have used DC-based vaccines loaded with an allogeneic heat shock-conditioned melanoma cell lysate in the treatment of advanced stage patients in a series of clinical trials. In these studies, 60% of treated patients showed immunological responses which correlated positively with improved survival. Considering the relevance of ovarian cancer and the promising results of our DC-based vaccine, we show here that heat shock-conditioned cell lysates derived from ovarian epithelial carcinoma cell lines have the potential to induce the phenotypic and functional maturation of human DC, which in turn, is able to induce an efficient CD4+ and CD8+ T cell-mediated immune responses against ovarian cancer cell lines in vitro. In summary, OEC heat shock-conditioned cell lysate-loaded DCs may be considered for future combined immunotherapy approaches against ovarian tumors.

MicroRNA-377-3p targeting MMP-16 inhibits ovarian cancer cell growth, invasion, and interstitial transition

“…Ovarian cancer (OC) is one of the most common cancers in women, with an incidence rate of 3-12/100,000. OC is characterized by rapid spread and high mortality rates (1)(2)(3). The development of drug resistance contributes to this to high mortality rate, which may be related to the increased expression of extracellular matrix (ECM) protein and drug transporters (4).…”

Vitexin attenuates epithelial ovarian cancer cell viability and motility in vitro and carcinogenesis in vivo via p38 and ERK1/2 pathways related VEGFA

“…Epithelial ovarian cancer (EOC) is a serious type of ovarian tumor that occurs worldwide and affects 3-12/100,000 women per year. EOC is characterized by high mortality rates and there is no effective routine treatment for the advanced stages of this disease (1)(2)(3). The leading cause of relapse and death in EOC patients is chemoresistance.…”

Haptoglobin Induces a Specific Proteomic Profile and a Mature-Associated Phenotype on Primary Human Monocyte-Derived Dendritic Cells

“…Among the proteins induced in the proteome of in vitro generated DCs by the stimulation with HP, we found several proteins with previously described functions associated with antigen processing and presentation (CD1A, CD1C, HLA-DRB1, HLA-DRB5, HLA-DQB1, HLA-B, HLA-C, TAP2, and AZGP1). A higher expression of MHC class I and II molecules is a well-known hallmark of DC maturation [5,16,18,40]. In this context, the finding of several exclusive and more abundant proteins associated with antigen processing and presentation processes correlates with a more mature phenotype induced by HP.…”