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  • Review Article
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Immunotherapy for ovarian cancer: towards a tailored immunophenotype-based approach

Nature Reviews Clinical Oncology (2024)Cite this article

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Abstract

Despite documented evidence that ovarian cancer cells express immune-checkpoint molecules, such as PD-1 and PD-L1, and of a positive correlation between the presence of tumour-infiltrating lymphocytes and favourable overall survival outcomes in patients with this tumour type, the results of trials testing immune-checkpoint inhibitors (ICIs) in these patients thus far have been disappointing. The lack of response to ICIs can be attributed to tumour heterogeneity as well as inherent or acquired resistance associated with the tumour microenvironment (TME). Understanding tumour immunobiology, discovering biomarkers for patient selection and establishing optimal treatment combinations remains the hope but also a key challenge for the future application of immunotherapy in ovarian cancer. In this Review, we summarize results from trials testing ICIs in patients with ovarian cancer. We propose the implementation of a systematic CD8+ T cell-based immunophenotypic classification of this malignancy, followed by discussions of the preclinical data providing the basis to treat such immunophenotypes with combination immunotherapies. We posit that the integration of an accurate TME immunophenotype characterization with genetic data can enable the design of tailored therapeutic approaches and improve patient recruitment in clinical trials. Lastly, we propose a roadmap incorporating tissue-based profiling to guide future trials testing adoptive cell therapy approaches and assess novel immunotherapy combinations while promoting collaborative research.

Key points

  • Ovarian cancer is an immunogenic malignancy, although the trials of immune-checkpoint inhibitors (ICIs) performed thus far have had modest response rates.

  • Triplet combinations of PARP inhibitors, anti-angiogenic agents and ICIs hold promise as a treatment option regardless of BRCA1/2 status; however, further studies are needed to define the optimal treatment schedule and account for the potentially higher risk of toxicities.

  • Adoptive cell therapies using T cells are feasible and have therapeutic potential in patients with ovarian cancer.

  • Novel combinations modulating the tumour myeloid compartment could be effective as salvage therapies for patients with immune-excluded or immune-deserted tumours as well as those resistant to ICIs.

  • The CD8+ tumour infiltrating lymphocyte immunophenotype could provide a rational and easy-to-implement biomarker to better select patients with ovarian cancer for next-generation immunotherapy combinations.

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Fig. 1: Proposed roadmap for personalized immunotherapies in ovarian cancer.

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Acknowledgements

D.D.L. receives support from the Ludwig Institute for Cancer Research and is the recipient of the Department of Defense (DOD) Early Career Investigator (ECI) W81XWH2210703 Award OC210038. Any views, opinions, findings, conclusions, or recommendations expressed in this material are solely those of the authors and do not necessarily reflect those of DOD.

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Author notes

  1. These authors contributed equally: Eleonora Ghisoni, Matteo Morotti.

Authors and Affiliations

  1. Department of Oncology, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland

    Eleonora Ghisoni, Matteo Morotti, Apostolos Sarivalasis, Alizée J. Grimm, Denarda Dangaj Laniti & George Coukos

  2. Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne (UNIL), Lausanne, Switzerland

    Eleonora Ghisoni, Matteo Morotti, Alizée J. Grimm, Lana Kandalaft, Denarda Dangaj Laniti & George Coukos

  3. Agora Cancer Research Center, Lausanne, Switzerland

    Eleonora Ghisoni, Matteo Morotti, Alizée J. Grimm, Denarda Dangaj Laniti & George Coukos

  4. Center of Experimental Therapeutics, Department of Oncology, Lausanne University Hospital, Lausanne, Switzerland

    Lana Kandalaft

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Contributions

E.G. and M.M. researched data for and wrote the article. G.C. and D.D.L. provided supervision and made substantial contributions to discussion of the content. All the authors reviewed and/or edited the manuscript before submission.

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Correspondence to George Coukos.

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Competing interests

M.M. is currently an employee of the CDR-Life company. A.S. has been a consultant and advisory board member for AstraZeneca, Bristol-Myers Squibb, Celgene, Eisai, GSK-Tesaro, MSD, Novartis, Roche and Seagen; received research support from AstraZeneca and Roche; and received institutional travel and congress support from Amgen, AstraZeneca, Celgene, Clovis, GSK-Tesaro, MSD, Novartis, Pfizer, Roche and Seagen. D.D.L. has received a grant from F. Hoffmann-La Roche AG. G.C. has received grants, research support or has been a co-investigator in clinical trials by Boehringer Ingelheim, Bristol-Myers Squibb, F. Hoffmann-La Roche AG, Iovance and Tigen Pharma. Lausanne University Hospital (CHUV) has received honoraria for advisory services that G.C. has provided to AstraZeneca, EVIR and Genentech. Patents related to the NeoTIL technology from the laboratory of G.C. have been licensed by the Ludwig Institute, on behalf of the University of Lausanne and the CHUV, to Tigen Pharma. G.C. has received royalties from the University of Pennsylvania for a CAR T cell product licensed to Novartis and Tmunity Therapeutics. E.G., A.J.G. and L.K. declare no competing interests.

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Nature Reviews Clinical Oncology thanks J. Hamanishi, J. Lederman and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Ghisoni, E., Morotti, M., Sarivalasis, A. et al. Immunotherapy for ovarian cancer: towards a tailored immunophenotype-based approach. Nat Rev Clin Oncol (2024). https://doi.org/10.1038/s41571-024-00937-4

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