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Clinical correlates for immune checkpoint therapy: significance for CNS malignancies
Nivedita M Ratnam1, Stephen C Frederico1, Javier A Gonzalez1
1Neuro-Oncology Branch, CCR, NCI, National Institutes of Health, Bethesda, Maryland, USA.
Abstract:
Immune checkpoint inhibitors (ICIs) have revolutionized the field of cancer immunotherapy. Most commonly, inhibitors of PD-1 and CTLA4 are used having received approval for the treatment of many cancers like melanoma, non-small-cell lung carcinoma, and leukemia. In contrast, to date, clinical studies conducted in patients with CNS malignancies have not demonstrated promising results. However, patients with CNS malignancies have several underlying factors such as treatment with supportive medications like corticosteroids and cancer therapies including radiation and chemotherapy that may negatively impact response to ICIs. Although many clinical trials have been conducted with ICIs, measures that reproducibly and reliably indicate that treatment has evoked an effective immune response have not been fully developed. In this article, we will review the history of ICI therapy and the correlative biology that has been performed in the clinical trials testing these therapies in different cancers. It is our aim to help provide an overview of the assays that may be used to gauge immunologic response. This may be particularly germane for CNS tumors, where there is currently a great need for predictive biomarkers that will allow for the selection of patients with the highest likelihood of responding.
Insights
Immune checkpoint inhibitors (ICIs) show promise in cancer immunotherapy but face challenges in CNS malignancies. This review explores assays to measure immune response, aiding biomarker development for better patient selection.
Area of Science:
- Immunology
- Oncology
- Neuro-oncology
Background:
- Immune checkpoint inhibitors (ICIs), targeting PD-1 and CTLA-4, have transformed cancer immunotherapy for various malignancies.
- Clinical trials of ICIs in CNS malignancies have yielded limited success, potentially due to factors like corticosteroid use, radiation, and chemotherapy.
- Reliable assays to confirm an effective immune response to ICIs are still under development.
Purpose of the Study:
- To review the history and correlative biology of ICI therapy in clinical trials across different cancer types.
- To provide an overview of assays for gauging immunologic response to ICIs.
- To address the need for predictive biomarkers in CNS tumors to identify likely responders.
Main Methods:
- Review of existing literature on immune checkpoint inhibitor therapy.
- Analysis of correlative biology studies from clinical trials.
- Identification and discussion of assays for measuring immunologic response.
Main Results:
- ICIs have demonstrated significant efficacy in several cancers but show limited benefit in CNS malignancies.
- Factors inherent to CNS tumor treatment may impede ICI efficacy.
- A gap exists in validated assays for assessing ICI-induced immune responses.
Conclusions:
- Further research is needed to overcome ICI resistance in CNS tumors.
- Development of robust predictive biomarkers is crucial for optimizing ICI therapy in neuro-oncology.
- Standardized assays are required to reliably measure immune responses to ICIs.
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