Objective The value of cell lines for pre-clinical work lies in choosing those with similar characteristics. Selection of cell lines is typically based on patient history, histological subtype at diagnosis, mutation patterns, or signaling pathways. Although recent studies established consensus regarding molecular characteristics of ovarian cancer cell lines, data on in vivo tumorigenicity remains only sporadically available, impeding translation of in vitro work to xenograft models. Methods We introduced 18 ovarian cancer cell lines into athymic nude mice through subcutaneous, intraperitoneal, and ovary intrabursal routes, and observed tumor development over 6 weeks. We also profiled cell line gene expression and identified differentially expressed gene sets based on their ability to form tumors in the subcutaneous or intraperitoneal locations. Representative cell lines were further subjected to proteomic analyses. Results Ovarian cancer cell lines showed variable ability to grow in mice when implanted subcutaneous, intraperitoneal, or intrabursal. While some cell lines grew well in both SC and IP locations, others showed a strong propensity to grow in one location only. Gene expression profiles suggested that cell lines showing preference for IP growth had gene expression patterns more similar to primary tumors. Conclusions We report the tumorigenicity of 17 human ovarian cancer cell lines and one mouse cell line in three distinct anatomical locations, and associated gene networks. Growth patterns and histopathology, linked to molecular characteristics, provide a valuable resource to the research community, and better guide the choice of cell lines for in vitro studies to translate efficiently into xenograft testing.

Ovarian cancer is the leading cause of death among gynecological neoplasms, with an estimated 14,000 deaths in 2019. First-line treatment options center around a taxane and platinum-based chemotherapy regimen. However, many patients often have recurrence due to late stage diagnoses and acquired chemo-resistance. Recent approvals for bevacizumab and poly (ADP-ribose) polymerase inhibitors have improved treatment options but effective treatments are still limited in the recurrent setting. Immunotherapy has seen significant success in hematological and solid malignancies. However, effectiveness has been limited in ovarian cancer. This may be due to a highly immunosuppressive tumor microenvironment and a lack of tumor-specific antigens. Certain immune cell subsets, such as regulatory T cells and tumor-associated macrophages, have been implicated in ovarian cancer. Consequently, therapies augmenting the immune response, such as immune checkpoint inhibitors and dendritic cell vaccines, may be unable to properly enact their effector functions. A better understanding of the various interactions among immune cell subsets in the peritoneal microenvironment is necessary to develop efficacious therapies. This review will discuss various cell subsets in the ovarian tumor microenvironment, current immunotherapy modalities to target or augment these immune subsets, and treatment challenges.

Purpose: Ovarian cancer is the most lethal gynecologic cancer and intrinsically resistant to checkpoint immunotherapies. We sought to augment innate immunity, building on previous work with interferons and monocytes. Experimental Design: Preclinical experiments were designed to define the mechanisms of cancer cell death mediated by the combination of interferons alpha and gamma with monocytes. We translated these preclinical findings into a phase I trial of autologous IFN-activated monocytes administered intraperitoneally to platinum-resistant or -refractory ovarian cancer patients. Results: Interferon (IFN)-treated monocytes induced caspase 8-dependent apoptosis by the proapoptotic tumor necrosis factor-related apoptosis inducing ligand (TRAIL) and mediated by the death receptors 4 and 5 (DR4 and DR5, respectively) on cancer cells. Therapy was well tolerated with evidence of clinical activity, as 2/9 evaluable patients had a partial response (PR) by RECIST criteria, and 1 additional patient had a CA-125 response. Upregulation of monocyte-produced TRAIL and cytokines was confirmed in peripheral blood. Long-term responders had alterations in innate and adaptive immune compartments. Conclusions: Given the mechanism of cancer cell death, and the acceptable tolerability of the clinical regimen, this platform presents a possibility for future combination therapies to augment anti-cancer immunity.