Monocyte reprogramming by nociceptors impedes T cell-mediated tumor immunity

Area of Science:

• Neuroimmunology
• Cancer Biology
• Oncology

Background:

• Nociceptors, pain-sensing neurons, interact with immune cells and influence immune responses.
• Myeloid-derived suppressor cells (MDSCs) are linked to impaired anti-tumor immunity and are prevalent in bladder cancer.

Purpose of the Study:

• To investigate the role of nociceptors in bladder cancer progression and immune evasion.
• To determine if nociceptors induce immunosuppressive myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment.

Main Methods:

• Utilized an orthotopic mouse model of urinary bladder carcinoma.
• Examined tumor innervation, monocyte infiltration, and MDSC differentiation.
• Assessed the impact of nociceptor ablation or inhibition on tumor growth and T cell responses.
• Investigated monocyte depletion effects in the presence of nociceptors.

Main Results:

• Incipient bladder tumors showed increased nociceptor innervation and monocyte infiltration, leading to MDSC formation.
• Nociceptors were crucial for establishing an immunosuppressive tumor microenvironment early in tumor development.
• Nociceptor inhibition or ablation prevented MDSC formation and promoted T cell-mediated tumor rejection.
• Monocyte depletion also led to tumor rejection in mice with intact nociceptors.

Conclusions:

• Urothelial tumors exploit a neuro-immune axis, involving nociceptors, to evade anti-tumor immunity.
• Nociceptors induce immunosuppressive MDSCs, contributing to bladder cancer progression.
• Targeting nociceptors represents a potential therapeutic strategy for bladder cancer treatment.