Immunotherapy in rare ovarian cancer

Abstract

Purpose of reviewOvarian cancer (OC) is a heterogeneous disease and a mounting body of evidence shows that a 'one-sizefits-all' approach is obsolete. Differences in epidemiology, tumor biology, genetic profiles and treatment responses of these different types necessitate a tumor and patient-specific approach. Ninety percentage consists of epithelial OC with 70% being high-grade serous OC. The other rarer subtypes are low-grade serous (5%), clear cell (12%), endometrioid (11%) and mucinous carcinoma (3%). The remaining 10% are nonepithelial rare OCs: germ cell (3%) and sex-cord stromal tumors (7%). Recent findingsOver the past few decades, the 5-year survival rates have only improved modestly, therefore novel therapies are urgently needed. Recently, immunotherapy has been introduced into clinical practice in a number of solid tumors. Although preclinical data confirm the presence of an immunogenic microenvironment in a number of ovarian tumor types, no single-agent immune checkpoint inhibitor has been approved hitherto. Identifying suitable treatment combinations, adequate patient selection and thus correct implementation of immunotherapy remain major challenges.

Integrated clinical characteristics and omics analysis identifies a ferroptosis and iron-metabolism-related lncRNA signature for predicting prognosis and therapeutic responses in ovarian cancer

“…The above findings suggest that the poorer prognosis of high-risk patients is due to higher immunosuppression in the tumour microenvironment, and these differences contribute to tumour progression. In addition, Immunotherapies based on checkpoint inhibitors have improved the survival of patients with OC [ 39 ]. Our results suggest significant differences in the expression of immune checkpoint related genes in different groups, indicating differences in immunotherapy sensitivity.…”

Profiling the immune landscape in mucinous ovarian carcinoma

“…In the context of immune checkpoint inhibition, current biomarkers thought to predict response include high tumor mutational burden, mismatch repair deficiency (MMRd)/microsatellite instability, high CD8+ T cell density, and PD-L1 expression [3]. Ovarian cancers in general have a lower tumor mutational burden relative to immunotherapyresponsive cancers such as melanoma or non-small cell lung cancer [4][5][6].…”

“…In HGSC, the C2-IMM molecular subtype is characterized as immunoreactive, and patients with these tumors have better survival outcomes [ 9 , 10 ]. Clear cell ovarian carcinoma may be more amenable to immune therapy which could potentially relate to ARID1A loss [ 3 ]. In a series of 184 MOCs, <1% of tumors had high tumor mutational burden or MMRd, which bodes poorly for single agent immune checkpoint inhibition [ 11 ].…”

Insights into ovarian cancer care: report from the ANZGOG Ovarian Cancer Webinar Series 2020

“…A major focus of the webinar series was treatment of the most fatal and frequent ovarian cancer subtypes. Treatment of the relatively rare subtypes, including low-grade serous, clear cell and mucinous and other non-epithelial carcinoma, for which there may be fertility sparing treatment options, was not within the scope of this webinar series, and has been recently reviewed elsewhere [ 6 ].…”