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

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2023 Jul 14

PMID 37446039

Authors

Anna Pawlowska

Anna Rekowska

Weronika Kurylo

Anna Panczyszyn

Jan Kotarski

Iwona Wertel

Affiliations

Soon will be listed here.

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.

Citing Articles

Targeting TOP2A in Ovarian Cancer: Biological and Clinical Implications.

Borella F, Fucina S, Seminara Y, Denti P, Ferraioli D, Bertero L Curr Oncol. 2024; 31(12):8054-8074.

PMID: 39727717 PMC: 11674396. DOI: 10.3390/curroncol31120594.

TIGIT CD4 regulatory T cells enhance PD-1 expression on CD8 T cells and promote tumor growth in a murine ovarian cancer model.

Chen F, Xu Y, Liu X, Dong N, Tian L J Ovarian Res. 2024; 17(1):252.

PMID: 39707532 PMC: 11660701. DOI: 10.1186/s13048-024-01578-y.

Unlocking the potential of immunotherapy in platinum-resistant ovarian cancer: rationale, challenges, and novel strategies.

Kefas J, Flynn M Cancer Drug Resist. 2024; 7:39.

PMID: 39534871 PMC: 11555186. DOI: 10.20517/cdr.2024.67.

Aberrant SWI/SNF Complex Members Are Predominant in Rare Ovarian Malignancies-Therapeutic Vulnerabilities in Treatment-Resistant Subtypes.

Ma Y, Field N, Xie T, Briscas S, Kokinogoulis E, Skipper T Cancers (Basel). 2024; 16(17).

PMID: 39272926 PMC: 11393890. DOI: 10.3390/cancers16173068.

Combining immunotherapy with PARP inhibitors. Is it possible to find the way through?.

Papageorgiou G, Skouteris N, Eleftheriou K, Kosmas C Immunotherapy. 2024; 16(16-17):999-1003.

PMID: 39268937 PMC: 11492662. DOI: 10.1080/1750743X.2024.2398412.

References

Fukumura D, Kloepper J, Amoozgar Z, Duda D, Jain R . Enhancing cancer immunotherapy using antiangiogenics: opportunities and challenges. Nat Rev Clin Oncol. 2018; 15(5):325-340. PMC: 5921900. DOI: 10.1038/nrclinonc.2018.29. View

Colombo N, Sessa C, Bois A, Ledermann J, McCluggage W, McNeish I . ESMO-ESGO consensus conference recommendations on ovarian cancer: pathology and molecular biology, early and advanced stages, borderline tumours and recurrent disease†. Ann Oncol. 2019; 30(5):672-705. DOI: 10.1093/annonc/mdz062. View

Shih I, Kurman R . Ovarian tumorigenesis: a proposed model based on morphological and molecular genetic analysis. Am J Pathol. 2004; 164(5):1511-8. PMC: 1615664. DOI: 10.1016/s0002-9440(10)63708-x. View

Langdon S, Herrington C, Hollis R, Gourley C . Estrogen Signaling and Its Potential as a Target for Therapy in Ovarian Cancer. Cancers (Basel). 2020; 12(6). PMC: 7352420. DOI: 10.3390/cancers12061647. View

Matsuyama H, Suzuki H, Nishimori H, Noguchi M, Yao T, Komatsu N . miR-135b mediates NPM-ALK-driven oncogenicity and renders IL-17-producing immunophenotype to anaplastic large cell lymphoma. Blood. 2011; 118(26):6881-92. DOI: 10.1182/blood-2011-05-354654. View

Failing J, Dudek O, Marin Acevedo J, Chirila R, Dong H, Markovic S . Biomarkers of hyperprogression and pseudoprogression with immune checkpoint inhibitor therapy. Future Oncol. 2019; 15(22):2645-2656. DOI: 10.2217/fon-2019-0183. View

Nero C, Ciccarone F, Pietragalla A, Duranti S, Daniele G, Salutari V . Ovarian Cancer Treatments Strategy: Focus on PARP Inhibitors and Immune Check Point Inhibitors. Cancers (Basel). 2021; 13(6). PMC: 7999042. DOI: 10.3390/cancers13061298. View

Zhang X, He T, Li Y, Chen L, Liu H, Wu Y . Dendritic Cell Vaccines in Ovarian Cancer. Front Immunol. 2021; 11:613773. PMC: 7874064. DOI: 10.3389/fimmu.2020.613773. View

Nguyen H, Phung C, Tran T, Pham T, Pham L, Nguyen T . Manipulating immune system using nanoparticles for an effective cancer treatment: Combination of targeted therapy and checkpoint blockage miRNA. J Control Release. 2020; 329:524-537. DOI: 10.1016/j.jconrel.2020.09.034. View

10.

Ukai M, Yokoi A, Yoshida K, Suzuki S, Shibata K, Kikkawa F . Extracellular miRNAs as Predictive Biomarkers for Glypican-3-Derived Peptide Vaccine Therapy Response in Ovarian Clear Cell Carcinoma. Cancers (Basel). 2021; 13(3). PMC: 7867082. DOI: 10.3390/cancers13030550. View

11.

Frelaut M, Le Tourneau C, Borcoman E . Hyperprogression under Immunotherapy. Int J Mol Sci. 2019; 20(11). PMC: 6600249. DOI: 10.3390/ijms20112674. View

12.

Heo Y . Mirvetuximab Soravtansine: First Approval. Drugs. 2023; 83(3):265-273. DOI: 10.1007/s40265-023-01834-3. View

13.

Walsh R, Sundar R, Lim J . Immune checkpoint inhibitor combinations-current and emerging strategies. Br J Cancer. 2023; 128(8):1415-1417. PMC: 10070427. DOI: 10.1038/s41416-023-02181-6. View

14.

Binnewies M, Pollack J, Rudolph J, Dash S, Abushawish M, Lee T . Targeting TREM2 on tumor-associated macrophages enhances immunotherapy. Cell Rep. 2021; 37(3):109844. DOI: 10.1016/j.celrep.2021.109844. View

15.

El-Daly S, Bayraktar R, Anfossi S, Calin G . The Interplay between MicroRNAs and the Components of the Tumor Microenvironment in B-Cell Malignancies. Int J Mol Sci. 2020; 21(9). PMC: 7246984. DOI: 10.3390/ijms21093387. View

16.

Chiou V, Burotto M . Pseudoprogression and Immune-Related Response in Solid Tumors. J Clin Oncol. 2015; 33(31):3541-3. PMC: 4622096. DOI: 10.1200/JCO.2015.61.6870. View

17.

Terp S, Pontoppidan Stoico M, Dybkaer K, Pedersen I . Early diagnosis of ovarian cancer based on methylation profiles in peripheral blood cell-free DNA: a systematic review. Clin Epigenetics. 2023; 15(1):24. PMC: 9926627. DOI: 10.1186/s13148-023-01440-w. View

18.

Kosaka N, Iguchi H, Ochiya T . Circulating microRNA in body fluid: a new potential biomarker for cancer diagnosis and prognosis. Cancer Sci. 2010; 101(10):2087-92. PMC: 11159200. DOI: 10.1111/j.1349-7006.2010.01650.x. View

19.

Banta K, Xu X, Chitre A, Au-Yeung A, Takahashi C, OGorman W . Mechanistic convergence of the TIGIT and PD-1 inhibitory pathways necessitates co-blockade to optimize anti-tumor CD8 T cell responses. Immunity. 2022; 55(3):512-526.e9. PMC: 9287124. DOI: 10.1016/j.immuni.2022.02.005. View

20.

Ferris R, Blumenschein Jr G, Fayette J, Guigay J, Colevas A, Licitra L . Nivolumab for Recurrent Squamous-Cell Carcinoma of the Head and Neck. N Engl J Med. 2016; 375(19):1856-1867. PMC: 5564292. DOI: 10.1056/NEJMoa1602252. View