Advancements in a novel model of autophagy and immune network regulation in radioresistance of cancer stem cells

Biomed Pharmacother. 2024 Oct:179:117420. doi: 10.1016/j.biopha.2024.117420. Epub 2024 Sep 9.

Abstract

Radiotherapy, a precise modality for treating malignant tumors, has undergone rapid advancements in primary and clinical research. The mechanisms underlying tumor radioresistance have become significant research. With the introduction and in-depth study of cancer stem cells (CSCs) theory, CSCs have been identified as the primary factor contributing to the development of tumor radioresistance. The "stemness" of CSCs is a biological characteristic of a small subset of cells within tumor tissues, characterized by self-renewal solid ability. This characteristic leads to resistance to radiotherapy, chemotherapy, and targeted therapies, driving tumor recurrence and metastasis. Another study revealed that cellular autophagy plays a pivotal role in maintaining the "stemness" of CSCs. Autophagy is a cellular mechanism that degrades proteins and organelles to generate nutrients and energy in response to stress. This process maintains cellular homeostasis and contributes to CSCs radioresistance. Furthermore, ionizing radiation (IR) facilitates epithelial-to-mesenchymal transition (EMT), vascular regeneration, and other tumor processes by influencing the infiltration of M2-type tumor-associated macrophages (TAMs). IR promotes the activation of the classical immunosuppressive "switch," PD-1/PD-L1, which diminishes T-cell secretion, leading to immune evasion and promoting radioresistance. Interestingly, recent studies have found that the immune pathway PD-1/PD-L1 is closely related to cellular autophagy. However, the interrelationships between immunity, autophagy, and radioresistance of CSCs and the regulatory mechanisms involved remain unclear. Consequently, this paper reviews recent research to summarize these potential connections, aiming to establish a theoretical foundation for future studies and propose a new model for the network regulation of immunity, autophagy, and radioresistance of tumor cells.

Keywords: Autophagy; CSCs; Immunity; Radioresistance; Radiotherapy.

Publication types

  • Review

MeSH terms

  • Animals
  • Autophagy*
  • Epithelial-Mesenchymal Transition
  • Humans
  • Neoplasms* / immunology
  • Neoplasms* / pathology
  • Neoplasms* / radiotherapy
  • Neoplastic Stem Cells* / immunology
  • Neoplastic Stem Cells* / pathology
  • Neoplastic Stem Cells* / radiation effects
  • Radiation Tolerance*
  • Tumor Microenvironment / immunology