Senescence markers: Predictive for response to checkpoint inhibitors
Abstract
Recent studies suggest that the age-related remodeling of the immune system, known as immunosenescence, could impact the efficacy of immune checkpoint inhibitors in leukemia or nonsmall cell lung cancer. We investigated whether senescence markers can predict response to checkpoint inhibitor therapy in melanoma patients. The peripheral blood of patients with newly diagnosed, untreated metastatic melanoma was analyzed by flow cytometry to correlate the frequency of senescence markers with clinical response as measured by RECIST after 12 weeks of treatment with immune checkpoint inhibitors. The loss of surface markers CD27 and CD28 or the expression of Tim-3 and CD57 on T cells was associated with resistance to checkpoint inhibitor blockade, presenting these phenotypes as possible predictive biomarkers for checkpoint inhibitor therapy. Immunosenescence seems to impact on the response to checkpoint inhibitor therapy in melanoma patients. Thus, lymphocyte phenotyping for senescence markers, with the introduction of immunosenescence panels, could be predictive for checkpoint inhibitor response.
Abstract
What's new?
Immune checkpoint inhibitors (ICIs) block checkpoint proteins on immune cells and certain cancer cell types, thereby facilitating immune attack on cancer cells. Some cancer patients, however, readily develop resistance to ICIs. In the present study, the authors analyzed peripheral blood samples from patients with newly diagnosed, untreated metastatic melanoma, revealing that the loss of senescence markers on peripheral blood mononuclear cells is correlated with clinical response to ICI therapy. Affected surface markers included CD27, CD28, Tim-3 and CD57. The findings could have implications for the development of methods to identify ICI non-responders, helping avoid unnecessary toxicity.
