Helper innate lymphoid cells as cell therapy for cancer

Although the first cancer immunotherapy was given in the clinic more than a century ago, this line of treatment has remained more of a distant goal than a practical therapy due to limited understanding of the tumour microenvironment and the mechanisms at play within it, which led to failures of numerous clinical trials. However, in the last two decades, the immune checkpoint inhibitors (ICIs) and chimeric antigen receptor-T cell therapies have revolutionized the treatment of cancer and provided proof-of-concept that immunotherapies are a viable option. So far, immunotherapies have majoritarily focused on utilizing T cells; however, T cells are not autonomous but rather function as part of, and therefore are influenced by, a vast cast of other immune cells, including innate lymphoid cells (ILCs). Here, we summarize the role of ILCs, especially helper ILCs, in tumour development, progression and metastasis, as well as their potential to be used as immunotherapy for cancer. By reviewing the studies that used helper ILCs as adoptive cell therapy (ACT), we highlight the rationale behind considering these cells as novel ACT for cancer as well as identify open questions and areas for future research.