Immune Checkpoint Inhibitors in Epithelial Ovarian Cancer: An Overview on Efficacy and Future Perspectives

Abstract

Epithelial ovarian cancer (EOC) is the leading cause of death among gynecological cancers. Despite improvements in medical treatments, the prognosis for EOC remains poor, and there is an urgent need for new therapeutic strategies. Immune checkpoint inhibitors (CPIs) have dramatically improved survival of several cancers and are under evaluation in OC. Unfortunately, CPIs have shown globally unsatisfactory results. The aim of this manuscript is to critically review the results from early-phase trials with CPIs in terms of safety and activity, discuss the possible reasons for disappointing results and the new therapeutic approaches to improve patient outcomes. However, despite the success of immunotherapy in other malignancies such as in melanoma, non-small cell lung cancer (NSCLC) and urothelial cancers [25,26], the use of antibodies inhibiting the immune checkpoint programmed cell death (PD-1) or its ligand (PD-L1) obtained modest results in EOC so far, with median response rates of 10% up to 15% [18][19][20]27].Interestingly, the combination of the anti-PD1 nivolumab and the anti-lymphocyte-associated protein 4 (anti-CTLA4) ipilimumab showed promising results in platinum-resistant EOC at six-month interim analyses with an overall response rate (ORR) of 34% (doubling the results of nivolumab monotherapy). However, final results are still awaited [28].As a consequence, no immunotherapeutic agent has obtained regulatory approval for EOC thus far. PD1/PD-L1

Comprehensive analysis of prognostic gene signatures based on immune infiltration of ovarian cancer

“…Numerous evidences support that OV is an immunogenic tumour [9,10] and immunotherapy is an efficient strategy due to its highly targeted on the immune checkpoints [5,11]. Besides, the prognostic assessment of immune system in OV has already been verified by previous researches [12][13][14]. Thus, it is pivotal to find out immune-related prognostic features in the treatment of OV.…”

Increased canonical NF-kappaB signaling specifically in macrophages is sufficient to limit tumor progression in syngeneic murine models of ovarian cancer

“…The therapeutic potential of targeting cells in the tumor microenvironment (TME) that support tumor growth and metastasis is being increasingly recognized. Overcoming T cell exhaustion by tumor cells via checkpoint inhibitor therapy has led to durable responses in some solid tumor types, but ovarian cancer patients have shown relatively poor response rates at least in part due to low numbers of tumor-infiltrating T cells [ 3 ]. Tumor-associated macrophages (TAMs) are highly enriched in the TME and have emerged as an attractive alternative target for therapy.…”

Brain Metastases from Ovarian Cancer: Current Evidence in Diagnosis, Treatment, and Prognosis

“…Currently, the immunological profile of BMs from OC has been investigated in 2 cases only, and, as previously mentioned, these brain lesions showed a high mutational burden and increased PD-L1 expression compared with primary tumors [71]. In fact, some data suggested a role of features like the clear cell histotype, PD-L1 expression by cancer cells, BRCA status, microsatellite instability, and tumor mutational burden in predicting OC response to immunotherapy [131]. These markers could help to identify patients who might benefit from immunotherapy and thus be evaluated in future studies focused on OC BMs.…”