Unlocking the power of innate lymphoid cell plasticity in the tumor microenvironment: A revolutionary pathway for cancer immunotherapy

Innate lymphoid cells (ILCs) are emerging as powerful players in the immune system, capable of dramatically influencing tumor immunity. Their extraordinary plasticity, which allows them to adapt to dynamic changes in the tumor microenvironment, positions them as a double-edged sword in cancer immunotherapy. While they can drive anti-tumor immune responses, they can also promote tumor progression under certain conditions. In this review, we delve into the multifaceted roles of ILCs—focusing on ILC1, ILC2, and ILC3—and explore how their functional plasticity can be harnessed to shift their activities from immune suppression to potent anti-tumor actions. We highlight groundbreaking therapeutic strategies aimed at modulating ILC plasticity, such as metabolic reprogramming, cytokine therapy, and CAR-ILC1 therapy, each designed to enhance the anti-tumor potential of these cells. Despite the immense promise, challenges remain, including immune suppression within the TME and the short-lived efficacy of cytokines. However, targeting ILC plasticity offers a transformative approach to overcome these hurdles, presenting an opportunity to personalize cancer treatment and create tailored immunotherapies that dynamically modulate the immune response. This review underscores the game-changing potential of ILC-based therapies and provides insights into the next generation of cancer immunotherapies that could revolutionize the fight against cancer.