Immunologic Correlates in the Course of Treatment With Immunomodulating Antibodies

Monoclonal antibodies (Ab) targeting immune checkpoints like CTLA-4 or PD-1 have come of age in the treatment of metastatic melanoma and further approvals are expected for other malignancies like lung and renal cell cancer as well. However, the majority of patients still do not experience clinical benefit upon these therapies. Moreover, immune-related side effects and the costs of these therapies prompt the search for their precise mode of action and for biomarker discovery. Here, we describe different classes of immunologic correlates such as pharmacodynamic changes observed in all treated patients, correlates with response during treatment (surrogate markers) or at the time-point of tumor assessment, as well as predictive markers for response and for immune-related adverse events. This review gives an overview of available data about correlates analyzed in the serum, all in immune cell subsets in the peripheral blood or in tumor-infiltrating lymphocytes. We will discuss how to prospectively validate and integrate these parameters for routine assessment of patients in daily clinical practice and give an outlook on promising future directions of biomarker research. (C) 2015 Elsevier Inc. All rights reserved.