Extrinsic and Cell-Intrinsic Stress in the Immune Tumor Micro-Environment

Int J Mol Sci. 2024 Nov 19;25(22):12403. doi: 10.3390/ijms252212403.

Abstract

In continuously progressive tumor tissues, the causes of cellular stress are multiple: metabolic alterations, nutrient deprivation, chronic inflammation and hypoxia. To survive, tumor cells activate the stress response program, a highly conserved molecular reprogramming proposed to cope with challenges in a hostile environment. Not only cancer cells are affected, but stress responses in tumors also have a profound impact on their normal cellular counterparts: fibroblasts, endothelial cells and infiltrating immune cells. In recent years, there has been a growing interest in the interaction between cancer and immune cells, especially in difficult conditions of cellular stress. A growing literature indicates that knowledge of the molecular pathways activated in tumor and immune cells under stress conditions may offer new insights for possible therapeutic interventions. Counter-regulating the stress caused by the presence of a growing tumor can therefore be a weapon to limit disease progression. Here, we review the main pathways activated in cellular stress responses with a focus on immune cells present in the tumor microenvironment.

Keywords: cancer-related inflammation; hypoxia; metabolism; tumor micro-environment; tumor-associated macrophages.

Publication types

  • Review

MeSH terms

  • Animals
  • Humans
  • Neoplasms* / immunology
  • Neoplasms* / metabolism
  • Neoplasms* / pathology
  • Signal Transduction
  • Stress, Physiological*
  • Tumor Microenvironment* / immunology