Immunotherapies, which refocus an individual’s immune system to better fight disease, have shown promise in the treatment of cancer as well as other diseases. Current immunotherapy approaches include cytokines (protein or antibodies directed to specific cytokines), cancer vaccines, checkpoint proteins, and immune cell adaptive transfer.
Immune checkpoint therapy uses monoclonal antibodies that recognize proteins called immune checkpoints. Checkpoint proteins are either inhibitory or stimulatory, as they are involved in stopping cell signaling, which results in T cell exhaustion, or promoting the activation of T cells, respectively. In these therapies, monoclonal antibodies against the inhibitory proteins are designed to “release the brake” so that cells of the immune system (henceforth referred to as “immune cells”) see the cancerous cells as “bad”, allowing for their elimination. The first approved checkpoint therapies for melanoma are based on antibodies that recognize CD152 (CTLA-4), CD279 (PD-1), and CD274 (PD-L1), and their efficacy is being tested with other cancers. Current treatments are now looking to combine therapies such as PD-1 and PD-L1. Although T cells play a key role (especially CD8+ T cells), more data concerning the recruitment role by macrophages and DCs are also coming to light. In fact, in addition to the CD8 T cells’ killing properties, the roles of myeloid derived suppressor cells (MDSCs), NK cells, and M1 (tumor rejecting phenotype) macrophages are shown to be contributors in responsiveness to therapies.
Understanding the phenotypes of immune cells and hence proteins involved in fighting cancer is critical for studying these potential therapies, and several techniques are emerging as valuable in this research. Flow cytometry is an extremely powerful cell analysis technique for both cells in circulation and samples derived from solid tumors, able to deliver information on phenotypes as well as cell health (proliferation vs. apoptosis) using a mutiparametric approach. Multicolor immunohistochemistry (IHC) allows the discrimination of cells’ phenotypes and locations within a solid tumor. IHC studies have shown that when CD8+ T cells are found in close proximity to PD-L1+ macrophages, tumors are more responsive to checkpoint inhibitor therapies. Lastly, assays such as ELISA/ELISPOT or multiplex immunoassays (such as ProcartaPlex assays) allow the monitoring of secreted and shed proteins in patients. Cytokines and other proteins like IFNg, perforin, and granzyme B are examples of routinely monitored proteins.
Whether your research is focused on searching for and detecting the new immune checkpoints or exploring the novel functions of immune checkpoints, Thermo Fisher Scientific offers a wide range of research antibodies to help ensure your success, including over 1,000 antibodies targeting immune checkpoints for both human and mouse experiments. Our experienced custom service team can also save you time by developing antibodies to meet your specifications. For more detailed antibody product descriptions, see Immune Checkpoint Antibodies