Cancer cells are tricky.

In order for tumors to grow they must avoid detection and recognition by the immune system. A group at Stanford has recently shown that tumor cells evade detection by phagocytic cells in order to persist.

Phagocytic cells are immune cells, dedicated to detecting, ingesting, and destroying foreign particles (from bacteria, viruses, parasites, dead or dying cells, etc). Macrophages are a type of phagocytic cell that are key players in fighting infection and irregular cell growth.

How do cancer cells “hide” from the phagocytic cells?

Communication is key in the immune system. Presentation of membrane proteins on the surface of the cell is one mechanism used by immune cells to communicate. For instance, if a macrophage ingests and destroys a bacterium it can then present bacterial proteins on the surface of the cell (on MHC-II receptors) in order to communicate to the adaptive immune system to induce bacteria-specific antibodies or proliferation of bacteria-specific killer T-cells.

One way cancer cells evade the immune system is by taking advantage of this communication line. They can hide from the immune system by expressing membrane protein CD47. CD47 is a “don’t eat me” signal for phagocytic cells, like macrophages, that is expressed on a multitude of cells. Therefore, when CD47 is expressed on cancer cells instead of macrophages detecting abnormal cells and destroying them, CD47 detection prompts macrophages to release the cells they have grabbed.

Can we harness this knowledge to fight cancer?

Brilliant.

Researchers at Stanford published in PNAS this month that when they transplant human tumors into laboratory mice they can make them virtually disappear when treated with a single antibody masking CD47. By creating a monoclonal antibody to CD47, or a CD47-specific antibody, and administering this to mice with human tumors they enabled the phagocytosis of tumor cells and inhibited growth/metastasis in tumor cells. They found this with human breast, ovarian, colon, bladder, brain, liver, and prostate cancer samples.

Representative images of breast cancer engrafted mice treated with anti-CD47 monoclonal antibodies (IgG is a non-specific antibody used as a control).

(E) Anti-CD47monoclonal antibodies inhibited the growth of a second breast cancer sample. (F) Colon tumor growth was inhibited by anti-CD47 mAbs, as evaluated by tumor mass and bioluminescence. (G) Glioblastoma growth was inhibited by anti-CD47 mAb treatment. (H) Representative bioluminescence images of treated mice (again, IgG is a non-specific antibody used as a control).

Additionally, they found that increased CD47 mRNA expression levels in some solid tumors correlated with a decreased probability of patient survival. According to Krista Conger at the Stanford School of Medicine News: “It is the first antibody treatment shown to be broadly effective against a variety of human solid tumors, and the dramatic response – including some overt cures in the laboratory animals – has the investigators eagar to begin phase-1 and -2 human clinical trials within the next two years”. The professor of pathology Irving Weissman, MD, the corresponding author on this publication reports, “This shows conclusively that this protein, CD47, is a legitimate and promising target for human cancer therapy”. I’m pumped, are you pumped?



Willingham, S., Volkmer, J., Gentles, A., Sahoo, D., Dalerba, P., Mitra, S., Wang, J., Contreras-Trujillo, H., Martin, R., Cohen, J., Lovelace, P., Scheeren, F., Chao, M., Weiskopf, K., Tang, C., Volkmer, A., Naik, T., Storm, T., Mosley, A., Edris, B., Schmid, S., Sun, C., Chua, M., Murillo, O., Rajendran, P., Cha, A., Chin, R., Kim, D., Adorno, M., Raveh, T., Tseng, D., Jaiswal, S., Enger, P., Steinberg, G., Li, G., So, S., Majeti, R., Harsh, G., van de Rijn, M., Teng, N., Sunwoo, J., Alizadeh, A., Clarke, M., & Weissman, I. (2012). The CD47-signal regulatory protein alpha (SIRPa) interaction is a therapeutic target for human solid tumors Proceedings of the National Academy of Sciences DOI: 10.1073/pnas.1121623109