Immune Checkpoint Proteins

Members of the B7 family of immune checkpoint proteins bind to receptors belonging to the CD28 family and promote or inhibit T cell activation following antigenic peptide/MHC recognition by the TCR. The B7 and CD28 families include the immune checkpoint proteins, PD-L1, PD-1, and CTLA-4, which are some of the most highly investigated targets for cancer immunotherapy.

Butyrophilins are T cell co-inhibitory/co-stimulatory molecules that are structurally related to the B7 family of immune checkpoint proteins and appear to have similar immunomodulatory functions. For these reasons, they are currently being investigated as potential next generation immune checkpoint targets.

The SIRP/CD47 pathway is an innate immune checkpoint that suppresses the phagocytic activity of myeloid cells. CD47 is overexpressed in a variety of hematologic and solid tumor cancers, indicating that tumor cells may exploit this pathway to evade phagocytic destruction.

Depletion of tryptophan and kynurenine production by the kynurenine pathway can inhibit the functions of T cells and natural killer cells and promote the generation of regulatory T cells. As tumor cells or cells in the tumor microenvironment can express high levels of IDO and TDO2, two key enzymes that catalyze the initial and rate-limiting step in this pathway, inhibitors of these molecules are being investigated as potential immunotherapeutic drugs.

LAG-3 is an inhibitory immune checkpoint receptor that negatively regulates T cell activity and promotes the suppressive activity of regulatory T cells. This receptor is up-regulated on exhausted T cells and natural killer cells in cancer and is thought to contribute to their dysfunction, making it a target for immuno-oncology researchers.

Members of the LILRB subfamily are immune checkpoint receptors that can inhibit the functions of multiple immune cell types following activation. These receptors and their ligands are being investigated by immuno-oncology researchers as they can be up-regulated on tumor cells or immune cells present in the tumor microenvironment, allowing tumors to evade immune detection.

TIGIT, DNAM-1, CD96, and PVRIG are immune checkpoint receptors that share CD155/PVR and/or CD112/Nectin-2 as ligands, but mediate opposing effects on lymphocyte functions. While DNAM-1/CD226 acts as a co-stimulatory receptor, TIGIT, PVRIG, and CD96 function as co-inhibitory receptors on T cells and natural killer cells. As a result, these proteins are being explored as targets for cancer immunotherapy.

High level expression of TIM-3 on CD8⁺ T cells and natural killer cells is associated with an exhausted phenotype, and its expression on tumor-associated FoxP3⁺ regulatory T cells (Tregs) marks a subset of Tregs with enhanced suppressor functions and increased resiliency. Due to these characteristics, immuno-oncology researchers are investigating TIM-3 blockade to determine if they can improve anti-tumor immune responses.

As an alternative to immune checkpoint blockade to restore anti-tumor immune responses, agonists of co-stimulatory immune checkpoint receptors are also being explored. Many of these receptors belong to the TNF receptor superfamily and have been shown to be involved in enhancing the proliferation and effector functions of T cells and/or natural killer cells.

Although still used in the industry for protein purity analysis, SDS-PAGE is self-limiting in terms of sensitivity, reproducibility, and its semi-quantitative nature. As an alternative, we offer the fully automated Maurice capillary electrophoresis (CE)-SDS system.This application note outlines the advantages of using Maurice over standard SDS-PAGE analysis for protein purity characterization. 

The tumor microenvironment (TME) plays a central role in inhibiting anti-tumor immune responses. Use our new poster to learn about the key mechanisms by which tumor cells, tumor-derived exosomes, regulatory T cells, myeloid-derived suppressor cells (MDSCs), and tumor-associated macrophages (TAMs) mediate immunosuppression in the TME.

RNAscope technology enables the rapid and efficient detection of the co-expression profiles of any target mRNAs, including immune checkpoint targets and immune cell markers, with single-molecule sensitivity and high specificity in formalin-fixed, paraffin-embedded (FFPE) tissues. This technology can be combined with immunohistochemistry or immunofluorescence on the same slide for detecting target RNAs and proteins simultaneously.

Biotinylated proteins can be powerful tools for assessing protein-protein interactions or screening antibody or small molecule libraries for potential therapeutics. We now offer a wide assortment of Avi-tag biotinylated recombinant proteins for immune checkpoint targets.

Profiling the composition and function of immune cells in the tumor microenvironment (TME) may guide an improved response to immunotherapy and uncover novel therapeutic targets. This application note outlines how Simple Western™ assays on Wes can be used with Single-cell Westerns™ on Milo to profile the immune cell populations in your sample.

The Bio-Techne family brands, R&D Systems and Novus Biologicals, are committed to providing the highest quality antibodies to support your research. Analyze the expression of immune checkpoint proteins or their ligands using our wide selection of flow cytometry-validated antibodies.