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Review
. 2023 Jun 29;24(13):10859.
doi: 10.3390/ijms241310859.

Current Understanding on Why Ovarian Cancer Is Resistant to Immune Checkpoint Inhibitors

Anna Pawłowska  1 , Anna Rekowska  2 , Weronika Kuryło  2 , Anna Pańczyszyn  3 , Jan Kotarski  1 , Iwona Wertel  1
Affiliations
Review

Current Understanding on Why Ovarian Cancer Is Resistant to Immune Checkpoint Inhibitors

Anna Pawłowska et al. Int J Mol Sci. .

Abstract

The standard treatment of ovarian cancer (OC) patients, including debulking surgery and first-line chemotherapy, is unsatisfactory because of recurrent episodes in the majority (~70%) of patients with advanced OC. Clinical trials have shown only a modest (10-15%) response of OC individuals to treatment based on immune checkpoint inhibitors (ICIs). The resistance of OC to therapy is caused by various factors, including OC heterogeneity, low density of tumor-infiltrating lymphocytes (TILs), non-cellular and cellular interactions in the tumor microenvironment (TME), as well as a network of microRNA regulating immune checkpoint pathways. Moreover, ICIs are the most efficient in tumors that are marked by high microsatellite instability and high tumor mutation burden, which is rare among OC patients. The great challenge in ICI implementation is connected with distinguishing hyper-, pseudo-, and real progression of the disease. The understanding of the immunological, molecular, and genetic mechanisms of OC resistance is crucial to selecting the group of OC individuals in whom personalized treatment would be beneficial. In this review, we summarize current knowledge about the selected factors inducing OC resistance and discuss the future directions of ICI-based immunotherapy development for OC patients.

Keywords: PD-1/PD-L1; TIGIT; immune checkpoints; immunotherapy; microRNA; ovarian cancer; resistance.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The modes of action of selected ICPs and ICIs.
Figure 2
Figure 2
The main features of hot, intermediate, and cold tumors.
Figure 3
Figure 3
The factors triggering the OC resistance to ICI-based immunotherapy.
See this image and copyright information in PMC

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