Mistakes happen. It’s a fact of life, and when mistakes occur during cell replication, the body has mechanisms to catch these errors and destroy the defective cells. However, when this system fails, it can lead to tumor growth and to cancer.

One of the primary systems involved in tumor and cancer detection is the immune system, but these cells have found ways to escape the immune response. The typical cancer immunity cycle starts with tumor cells releasing tumor antigens to activate tumor-specific T cells. These T-cells then recognize cancer cells and induce cell death.

Immune evasion can occur through multiple mechanisms. For example, tumor cells may lose the ability to process and present antigens and/or they may overexpress cell surface markers or cytokines which suppress the immune response as one portion of the tumor microenvironment.

Tumors can escape immune recognition by upregulating PD-L1, an immunoinhibitory molecule, on their surface. This upregulation may be in response to IFN? produced by tumor-infiltrating lymphocytes in the tissue. Other proteins involved in immune evasion include, but are not limited to:

– NLRC5 has been found to be a critical co-activator of MHC-I gene expression.

– TAP1 downregulation has been shown to elicit immune escape in colorectal cancer.

– MUC1 and PD-L1 are upregulated in triple-negative breast cancer.

– JAK1 mutations in cancer cells can lead to loss of function and immune evasion.

– TGF?  upregulation in the tumor microenvironment promotes T-cell exclusion.

– TGF?, IL-10, IDO, and other immunosuppressive factors, as well as expression of PD-1, CTLA-4, LAG-3 are some mechanisms of breast cancer immune evasion.

In contrast to not presenting antigens, chronic exposure of antigens can lead to sustained expression of CTLA-4 and PD-1 in T-cells, dampening the ability of these cells to kill cancer or virus-infected cells. Evading/suppressing suppressive cells of the immune system appears to be a major mechanism of tumor immune escape.

Modern immunotherapy strategies include harnessing the body’s immune response to treat cancer. In order to develop such therapeutics, it is critical to understand cancer cell immune evasion. As research expands into decoding the immune evasion mechanisms of various cancer types, ProSci enables further discovery by providing antibodies against known and suspected proteins involved in immune evasion. Contact us to find out how we can help your research.

References

Beatty, G. L., & Gladney, W. L. (2014). Immune Escape Mechanisms as a Guide for Cancer Immunotherapy. Clinical Cancer Research, 21(4), 687–692. https://doi.org/10.1158/1078-0432.ccr-14-1860

Nicolini, A., Ferrari, P., Rossi, G., & Carpi, A. (2018). Tumour growth and immune evasion as targets for a new strategy in advanced cancer. Endocrine-Related Cancer, 25(11), R577–R604. https://doi.org/10.1530/erc-18-0142

Ling, A., Löfgren-Burström, A., Larsson, P., Li, X., Wikberg, M. L., Öberg, Ĺ., Stenling, R., Edin, S., & Palmqvist, R. (2017). TAP1 down-regulation elicits immune escape and poor prognosis in colorectal cancer. OncoImmunology, 6(11), e1356143. https://doi.org/10.1080/2162402x.2017.1356143

Maeda, T., Hiraki, M., Jin, C., Rajabi, H., Tagde, A., Alam, M., Bouillez, A., Hu, X., Suzuki, Y., Miyo, M., Hata, T., Hinohara, K., & Kufe, D. (2017). MUC1-C Induces PD-L1 and Immune Evasion in Triple-Negative Breast Cancer. Cancer Research, 78(1), 205–215. https://doi.org/10.1158/0008-5472.can-17-1636

Albacker, L. A., Wu, J., Smith, P., Warmuth, M., Stephens, P. J., Zhu, P., Yu, L., & Chmielecki, J. (2017). Loss of function JAK1 mutations occur at high frequency in cancers with microsatellite instability and are suggestive of immune evasion. PLOS ONE, 12(11), e0176181. https://doi.org/10.1371/journal.pone.0176181

Tauriello, D. V. F., Palomo-Ponce, S., Stork, D., Berenguer-Llergo, A., Badia-Ramentol, J., Iglesias, M., Sevillano, M., Ibiza, S., Cańellas, A., Hernando-Momblona, X., Byrom, D., Matarin, J. A., Calon, A., Rivas, E. I., Nebreda, A. R., Riera, A., Attolini, C. S.-O., & Batlle, E. (2018). TGF? drives immune evasion in genetically reconstituted colon cancer metastasis. Nature, 554(7693), 538–543. https://doi.org/10.1038/nature25492

Bates, J. P., Derakhshandeh, R., Jones, L., & Webb, T. J. (2018). Mechanisms of immune evasion in breast cancer. BMC Cancer, 18(1). https://doi.org/10.1186/s12885-018-4441-3