Targeting immune checkpoints in gynecologic cancer: updates & perspectives for pathologists
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Published on: August 18, 2023
Anne M Mills1, Tim N Bullock2, Kari L Ring3
1Department of Pathology, Division of Anatomic Pathology, University of Virginia, Charlottesville, VA, USA. amm7r@virginia.edu.
Abstract:
Checkpoint inhibitor-based immunotherapy is increasingly used in the treatment of gynecologic cancers, and most often targets the PD-1/PD-L1 axis. Pathologists should be familiar with the biomarkers required to determine candidacy for these treatments based on existing FDA approvals, including mismatch repair protein immunohistochemistry, microsatellite instability testing, tumor mutation burden testing, and PD-L1 immunohistochemistry. This review summarizes the rationale behind these treatments and their associated biomarkers and delivers guidance on how to utilize and readout these tests. It also introduces additional biomarkers which may provide information regarding immunotherapeutic vulnerability in the future such as neoantigen load; POLE mutation status; and immunohistochemical expression of immunosuppressive checkpoints like LAG-3, TIM-3, TIGIT, and VISTA; immune-activating checkpoints such as CD27, CD40, CD134, and CD137; enzymes such as IDO-1 and adenosine-related compounds; and MHC class I.
Insights
Checkpoint inhibitor immunotherapy, targeting the PD-1/PD-L1 axis, is vital for gynecologic cancers. Pathologists need to understand key biomarkers like PD-L1 IHC and MSI testing for patient selection.
Area of Science:
- Oncology
- Immunology
- Pathology
Background:
- Checkpoint inhibitor immunotherapy, primarily targeting the PD-1/PD-L1 axis, is increasingly utilized in gynecologic cancer treatment.
- Accurate biomarker assessment is crucial for determining patient eligibility for these advanced therapies.
Purpose of the Study:
- To review the rationale and current FDA-approved biomarkers for checkpoint inhibitor immunotherapy in gynecologic cancers.
- To provide guidance on the utilization and interpretation of these essential diagnostic tests.
- To introduce emerging biomarkers for predicting future immunotherapeutic response.
Main Methods:
- Review of existing literature and FDA approvals for immunotherapy biomarkers in gynecologic cancers.
- Summary of immunohistochemistry (IHC) and molecular testing methodologies.
- Discussion of novel biomarkers including neoantigen load, POLE status, and various immune checkpoint expressions.
Main Results:
- Established biomarkers for FDA-approved checkpoint inhibitors include mismatch repair protein IHC, microsatellite instability testing, tumor mutation burden testing, and PD-L1 IHC.
- These biomarkers are critical for patient selection and treatment guidance.
- Emerging biomarkers like LAG-3, TIM-3, TIGIT, VISTA, CD27, CD40, CD134, CD137, IDO-1, adenosine, and MHC class I show future potential.
Conclusions:
- Familiarity with current biomarkers is essential for pathologists managing gynecologic cancer patients receiving immunotherapy.
- Understanding these tests ensures optimal patient selection and treatment efficacy.
- Exploration of novel biomarkers will further refine immunotherapy strategies in gynecologic oncology.
