The AXL-mediated modulation of myeloid-derived suppressor cells (MDSC) in nasopharyngeal carcinoma

Yu Lv1, Jiahui Zhu1, Sichen Ge1

  • 1Department of Otorhinolaryngology Head and Neck Surgery, The First Affiliated Hospital of Bengbu Medical University, Bengbu, 233000, Anhui, China.

Insights

AXL receptor tyrosine kinase drives cancer progression and immune suppression. This study reveals AXL critically modulates myeloid-derived suppressor cells (MDSCs) in nasopharyngeal carcinoma, offering new immunotherapy targets.

Area of Science:

  • Oncology
  • Immunology
  • Molecular Biology

Background:

  • AXL receptor tyrosine kinase is implicated in cancer progression, metastasis, and immunotherapy resistance.
  • The precise role of AXL in the tumor immune microenvironment (TIME) and its impact on immune cells remains unclear.

Purpose of the Study:

  • To investigate the role of AXL in myeloid-derived suppressor cell (MDSC) differentiation and accumulation within the tumor immune microenvironment.
  • To elucidate the mechanisms by which AXL influences cytokine production and immune cell populations in nasopharyngeal carcinoma (NPC).

Main Methods:

  • Established AXL knockdown and overexpression cell lines via lentiviral infection.
  • Co-cultured cancer cells with peripheral blood mononuclear cells (PBMCs) to assess MDSC differentiation.
  • Measured cytokine levels (IL-6, GM-CSF) in culture supernatants.
  • Evaluated AXL expression and MDSC recruitment in murine NPC models.

Main Results:

  • AXL was identified as a critical regulator of MDSC differentiation and accumulation in NPC.
  • AXL modulates the TIME by influencing IL-6, GM-CSF, and Toll-like receptor levels.
  • A direct correlation was observed between AXL expression and MDSC recruitment in tumors.

Conclusions:

  • AXL plays a significant role in shaping the tumor immune microenvironment by controlling MDSC populations.
  • Targeting AXL presents a promising strategy for enhancing the efficacy of current cancer immunotherapies.
  • Understanding AXL's function in MDSC regulation offers novel therapeutic avenues for NPC and potentially other cancers.