Helper innate lymphoid cells as cell therapy for cancer

Abstract

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.

The IL-25/ILC2 axis promotes lung cancer with a concomitant accumulation of immune-suppressive cells in tumors in humans and mice

“…While the role of ILC2 cells in allergy and parasitic infections is now well-established, their role in cancer is still controversial ( 3 ). In a murine model of heterotopic lung cancer expressing IL-33, ILC2-deficient mice, which were generated by reconstituting their bone marrow with RORalpha -/- hematopoietic stem cells, showed increased tumor growth and metastasis, suggesting an anti-tumor role for IL-33-activated ILC2 cells ( 10 ).…”

“…ILC2 cells are known to be enriched in both human and mouse lung, and to be activated by IL-25 and IL-33 ( 2 ). The role of ILC2 cells in cancer is highly controversial with some studies showing they are pro-tumorigenic, while others report the opposite ( 3 , 4 ). In recent years, the number of publications reporting on the role of ILC2 cells in cancer contexts have grown exponentially ( 4 ).…”

Innate lymphoid cells—Underexplored guardians of immunity

“…The low abundance of peripheral blood ILCs pose extreme technical challenges for isolation and identification. Hence, robust methods for ex vivo expansion of ILC-progenitors from peripheral blood, bone marrow, or umbilical cord blood are urgently needed [ 42 , 71 , 73 ]. Of note, proof-of-concept studies show that human ILCs can be obtained from various sources, remain viable and functional under in vitro expansion conditions, offering interesting options for cell-based therapies similar to T or NK cells [ 73 ].…”