The field of oncology has been transformed by the approval and implementation of immune checkpoint inhibitors. Cancer cells can tamper with a variety of self-defense mechanisms, including upregulating expression of immune checkpoint molecules on cytotoxic T cells and natural killer (NK) cells, such as PD-1 and CTLA-4. Overexpression of these markers is associated with T cell exhaustion and allows for tumor cells to evade detection. Immune checkpoint inhibitors target these molecules, which restores immune surveillance and anti-tumor responses by T cells.
Flow cytometry has been crucial to the discovery and characterization of immune checkpoint molecules, especially in terms of defining the immune cell phenotypes associated with exhaustion and immune suppression. Researchers continue to refine their understanding of the mechanisms associated with immune checkpoint inhibitors working effectively to restore anti-tumor responses. Clinical flow cytometry has also been essential to the preclinical development of new or modified immune checkpoint inhibitors and in monitoring the efficacy of these inhibitors during treatment. The clinical usage of immune checkpoint inhibitors has been growing since the first anti-CTLA-4 monoclonal antibody was approved by the FDA in 2011 and the first anti-PD-1 monoclonal antibody was approved in 2014. Widespread usage of these and other therapies has revealed a growing problem of treatment resistance. New trials are underway to evaluate the efficacy of combination therapies, including combinations of immune checkpoint inhibitors and protocols that use these inhibitors alongside other experimental or existing cancer treatments.
Clinical flow cytometry continues to be instrumental to identifying other immune checkpoint molecules that could be targeted therapeutically, such as LAG-3 and IDO. Flow cytometry panels can now be created with high dimensional capacity and this capability allows scientists to evaluate the effect of experimental immune checkpoint inhibitors on multiple immune cell subsets in a single experiment. Flow cytometry can also be used to monitor immune cells and hematologic malignancies in peripheral blood and can be customized to examine which immune cells are present in solid tumor biopsies. Changes in inflammatory molecules within cells, such as levels of different interferons and TNF-alpha, can also be monitored using these comprehensive flow cytometry panels.
The advancement of immune checkpoint inhibitor-based therapies is intimately linked to improvements in flow cytometry hardware and reagents. This field not only promises to improve cancer treatment but has the potential to transform the treatment of other immune system disorders.