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Limitations and potential of immunotherapy in ovarian cancer.

ABSTRACT: Ovarian cancer (OC) is the third most common gynecological cancer and alone has an emergence rate of approximately 308,069 cases worldwide (2020) with dire survival rates. To put it into perspective, the mortality rate of OC is three times higher than that of breast cancer and it is predicted to only increase significantly by 2040. The primary reasons for such a high rate are that the physical symptoms of OC are detectable only during the advanced phase of the disease when resistance to chemotherapies is high and around 80% of the patients that do indeed respond to chemotherapy initially, show a poor prognosis subsequently. This highlights a pressing need to develop new and effective therapies to tackle advanced OC to improve prognosis and patient survival. A major advance in this direction is the emergence of combination immunotherapeutic methods to boost CD8⁺ T cell function to tackle OC. In this perspective, we discuss our view of the current state of some of the combination immunotherapies in the treatment of advanced OC, their limitations, and potential approaches toward a safer and more effective response.

SUBMITTER: Kumar S

PROVIDER: S-EPMC10803592 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Limitations and potential of immunotherapy in ovarian cancer.

Kumar Sandeep S Acharya Sayanti S Karthikeyan Mahalakshmi M Biswas Priyobrata P Kumari Sudha S

Frontiers in immunology 20240109

Ovarian cancer (OC) is the third most common gynecological cancer and alone has an emergence rate of approximately 308,069 cases worldwide (2020) with dire survival rates. To put it into perspective, the mortality rate of OC is three times higher than that of breast cancer and it is predicted to only increase significantly by 2040. The primary reasons for such a high rate are that the physical symptoms of OC are detectable only during the advanced phase of the disease when resistance to chemothe ...[more]

PMID: 38264664

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Project description:Elimination of cancer through early detection and treatment is the ultimate goal of cancer research and is especially critical for ovarian and other forms of cancer typically diagnosed at very late stages that have very poor response rates. Proteomics has opened new avenues for the discovery of diagnostic and therapeutic targets. Immunoproteomics, which defines the subset of proteins involved in the immune response, holds considerable promise for providing a better understanding of the early-stage immune response to cancer as well as important insights into antigens that may be suitable for immunotherapy. Early administration of immunotherapeutic vaccines can potentially have profound effects on prevention of metastasis and may potentially cure through efficient and complete tumor elimination. We developed a mass-spectrometry-based method to identify novel autoantibody-based serum biomarkers for the early diagnosis of ovarian cancer that uses native tumor-associated proteins immunoprecipitated by autoantibodies from sera obtained from cancer patients and from cancer-free controls to identify autoantibody signatures that occur at high frequency only in cancer patient sera. Interestingly, we identified a subset of more than 50 autoantigens that were also processed and presented by MHC class I molecules on the surfaces of ovarian cancer cells and thus were common to the two immunological processes of humoral and cell-mediated immunity. These shared autoantigens were highly representative of families of proteins with roles in key processes in carcinogenesis and metastasis, such as cell cycle regulation, cell proliferation, apoptosis, tumor suppression, and cell adhesion. Autoantibodies appearing at the early stages of cancer suggest that this detectable immune response to the developing tumor can be exploited as early-stage biomarkers for the development of ovarian cancer diagnostics. Correspondingly, because the T-cell immune response depends on MHC class I processing and presentation of peptides, proteins that go through this pathway are potential candidates for the development of immunotherapeutics designed to activate a T-cell immune response to cancer. To the best of our knowledge, this is the first comprehensive study that identifies and categorizes proteins that are involved in both humoral and cell-mediated immunity against ovarian cancer, and it may have broad implications for the discovery and selection of theranostic molecular targets for cancer therapeutics and diagnostics in general.

Dataset Information

Limitations and potential of immunotherapy in ovarian cancer.

Publications

Limitations and potential of immunotherapy in ovarian cancer.

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