Beyond the limits of current checkpoint blockade approaches: how spatial biology tools can help unlock cancer therapeutics
The interplay among tumor cells, the surrounding tissue, and infiltrating innate and adaptive immune cells create a distinct environment that varies depending on the tumor type, stage, host, and treatment history1. This complex ecosystem is called the tumor microenvironment (TME) and refers to the surrounding cellular and non-cellular components within a tumor core and its periphery. It includes various tissue cell types, an extracellular matrix, blood vessels, immune cells, fibroblasts, and signaling molecules that enable communication within the TME and between the TME and the rest of the body.
The tumor-immune microenvironment presents a complex and challenging landscape for cancer therapeutics.
The identification and understanding of immune checkpoint proteins that regulate immune responses have revolutionized the field of cancer care. Immune checkpoints serve as “brakes” on the immune system, preventing overactivation and potential damage to healthy tissues. They help maintain self-tolerance and protect against autoimmunity. However, cancer cells hijack these safety mechanisms to bypass immune recognition. Well-known immune checkpoint proteins include Programmed Death-1 (PD-1) and Programmed Death Ligand-1 (PD-L1): PD-1 is expressed on the surface of activated T cells (Figure 1), while PD-L1 is often upregulated on tumor cells and immune cells within the TME. When PD-1 on T cells binds to PD-L1 on tumor cells, it inhibits T cell activity and prevents effective anti-tumor immune responses.
The sequential immunofluorescence (seqIF™) protocol offers a powerful solution for designing and executing off-the-shelf, same-species antibody panels without needing antibody labeling. The COMET™ platform can unlock spatial data, enabling in-depth sample analyses at the single-cell level.
The future of cancer therapeutics: embracing spatial biology
Spatial biology tools are revolutionizing our understanding of the TME. By spatially profiling the expression of the immune checkpoints, researchers can identify immune-inhibitory signals, predict responses to checkpoint inhibitors, and design combination therapies to overcome resistance. By providing a comprehensive view of the spatial organization, cellular interactions, and immune landscape within tumors, these tools enable the development of novel therapeutic strategies and the optimization of existing treatment approaches. From identifying new immunotherapeutic targets to predicting treatment responses and monitoring therapeutic efficacy, spatial biology propels cancer therapeutics into a new era of precision and effectiveness.
- Learn how seqIF™ on COMET™ allows for rapid characterization of immune cells within the tumor microenvironment.
- Uncover composite images of each of the 22 markers on different TMAs.
- Discover HORIZON™ features.
- Hsieh WC et al. Spatial multi-omics analyses of the tumor immune microenvironment. J Biomed Sci. 29(1):96.doi: 10.1186/s12929-022-00879-y.
- Sharma P et al. The Next Decade of Immune Checkpoint Therapy. Cancer Discov. 2021. 11(4):838-857. doi: 10.1158/2159-8290.CD-20-1680.
- Pearce H. et al. Tissue-resident memory T cells in pancreatic ductal adenocarcinoma co-express PD-1 and TIGIT and functional inhibition is reversible by dual antibody blockade. Cancer Immunol Res. CIR-22-0121. doi: 10.1158/2326-6066.CIR-22-0121.