Clinical correlates for immune checkpoint therapy: significance for CNS malignancies.

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.