Tumor-related stress regulates functional plasticity of MDSCs

Area of Science:

• Immunology
• Oncology

Background:

• Myeloid-derived suppressor cells (MDSCs) are critical regulators of the tumor immune microenvironment.
• MDSCs suppress anti-tumor immunity, representing a significant barrier to effective cancer therapies.

Purpose of the Study:

• To review tumor-associated stress axes that influence MDSC development, accumulation, and immunosuppressive functions.
• To discuss current therapeutic strategies targeting these stress pathways to overcome MDSC-mediated immune suppression.

Main Methods:

• Literature review of studies investigating MDSC biology and tumor-associated stress.
• Synthesis of information on various stress pathways including oxidative, inflammatory, hypoxic, ER, metabolic, and therapy-induced stress.

Main Results:

• Diverse tumor-derived stressors, termed 'axes of stress,' orchestrate MDSC differentiation, expansion, and immunosuppressive programming.
• Specific stress axes discussed include reactive oxygen/nitrogen species, chronic inflammation, hypoxia, endoplasmic reticulum stress, metabolic stress, and therapy-associated stress.

Conclusions:

• Understanding these stress axes is crucial for deciphering MDSC heterogeneity and function in cancer.
• Targeting these tumor-associated stress pathways holds potential for pre-clinical therapeutic strategies to enhance anti-tumor immunity.