IL-1 and senescence: Friends and foe of EGFR neutralization and immunotherapy

Abstract

Historically, senescence has been considered a safe program in response to multiple stresses in which cells undergo irreversible growth arrest. This process is characterized by morphological and metabolic changes, heterochromatin formation, and secretion of inflammatory components, known as senescence-associated secretory phenotype (SASP). However, recent reports demonstrated that anti-cancer therapy itself can stimulate a senescence response in tumor cells, the so-called therapy-induced senescence (TIS), which may represent a temporary bypass pathway that promotes drug resistance. In this context, several studies have shown that EGFR blockage, by TKIs or moAbs, promotes TIS by increasing IL-1 cytokine production, thus pushing cells into a “pseudo-senescent” state. Today, senotherapeutic agents are emerging as a potential strategy in cancer treatment thanks to their dual role in annihilating senescent cells and simultaneously preventing their awakening into a resistant and aggressive form. Here, we summarize classic and recent findings about the cellular processes driving senescence and SASP, and we provide a state-of-the-art of the anti-cancer strategies available so far that exploits the activation and/or blockade of senescence-based mechanisms.

Comprehensive analysis of cellular senescence and immune microenvironment in papillary thyroid carcinoma

“…Among the cancer hallmarks suggested for the third edition in 2022, four new ones were added, including senescent cells [ 17 ]. Targeting the activation or inhibition of cellular senescence is beneficial for tumor immunotherapy [ 18 ]. Although several lines of evidence indicate that young adults with cancers demonstrate unique histological and survival heterogeneity, their biology is incompletely understood [ 19 , 20 ].…”