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 tumor microenvironment and the mechanisms at play within it, which lead to failures of numerous clinical trials. However, in the last two decades, the immune checkpoint inhibitors 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 tumor 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, we highlight the rationale behind considering these cells as novel adoptive cell therapy for cancer as well as identify open questions and areas for future research.

It is now clear that group 2 innate lymphoid cells (ILC2) play crucial and sometimes opposing roles in the lung, such as restoring barrier function and integrity after viral infections or, on the contrary, exacerbating inflammation and tissue damage in allergic asthma. However, their role in lung cancer is still unclear. Here, we report that human non-small cell lung cancer patients bear increased frequencies of ILC2s in tumors, normal lung tissue and peripheral blood (PB) as compared to PB from healthy donors (HDs). Frequencies of Foxp3+ regulatory T cells were also increased in NSCLC patients, concomitantly with ILC2s. In mice bearing heterotopic lung cancer, adoptive transfer of ILC2s led to increased tumor growth and reduced survival. The frequencies of monocytic myeloid-derived suppressor cells (M-MDSCs) were found to be increased in the tumors of mice that received ILC2s as compared to controls. Overall, our results indicate that ILC2 cells play a pro-tumoral role in lung cancer potentially by recruiting immune-suppressive cells to the tumors.