Advances in targeting the CD47/SIRPα "do not eat me" pathway for cancer therapy

A new editorial was recently published in Oncotarget's Volume 15, on July 10, 2024, entitled, "The advances in targeting CD47/SIRPα "do not eat me" axis and their ongoing challenges as an anticancer therapy."

As discussed in this paper, the growing understanding of the tumor immune microenvironment (TME) and its impact on treatment outcomes has led to advances in cancer therapy aimed at enhancing antitumor immune responses. While most current immunotherapies focus on T cells and immune checkpoint inhibitors (ICIs), there is increasing interest in targeting innate immune components, such as macrophages. Tumor-associated macrophages (TAMs) support tumor growth, metastasis, and angiogenesis, making them key targets for novel immunotherapies aimed at shifting the M2-like (pro-tumoral) macrophages to the M1-like (antitumoral) phenotype.

In their editorial, researchers Maria Gracia-Hernandez, Manasa Suresh, and Alejandro Villagra from Georgetown University Medical Center, highlight key phagocytosis checkpoints and "do not eat me" signals-;such as CD47, CD24, MHC-I, PD-L1, STC1, and GD2-;that have emerged as potential therapeutic targets. 

The authors note that many tumor types overexpress CD47 to evade phagocytosis by interacting with SIRPα on macrophages. The editorial also summarizes challenges in targeting CD47 and potential solutions to overcome these obstacles.

"Overall, our understanding of this significant 'do not eat me' pathway over the years has resulted in the development of novel therapies and strategies to boost innate antitumor activity."