Roles of IL-1 in Cancer: From Tumor Progression to Resistance to Targeted Therapies

Gelfo, Valerio; Romaniello, Donatella; Mazzeschi, Martina; Sgarzi, Michela; Grilli, Giada; Morselli, Alessandra; Manzan, Beatrice; Rihawi, Karim; Lauriola, Mattia

IL-1 belongs to a family of 11 members and is one of the seven receptor-agonists with pro-inflammatory activity. Beyond its biological role as a regulator of the innate immune response, IL-1 is involved in stress and chronic inflammation, therefore it is responsible for several pathological conditions. In particular, IL-1 is known to exert a critical function in malignancies, influencing the tumor microenvironment and promoting cancer initiation and progression. Thus, it orchestrates immunosuppression recruiting pro-tumor immune cells of myeloid origin. Furthermore, new recent findings showed that this cytokine can be directly produced by tumor cells in a positive feedback loop and contributes to the failure of targeted therapy. Activation of anti-apoptotic signaling pathways and senescence are some of the mechanisms recently proposed, but the role of IL-1 in tumor cells refractory to standard therapies needs to be further investigated.