Immunotherapy Mechanism of Esophageal Squamous Cell Carcinoma with the Effect of STK11/AMPK Signaling Pathway

Yang Xia1, Peng Wang1, Yunyao Ye1

  • 1Department of Oncology, Taizhou People's Hospital, Taizhou, 225300 Jiangsu Province, China.

Insights

Immunotherapy impacts esophageal squamous cell carcinoma (ESCC) by modulating the serine threonine protein kinase 11 (STK11)/Adenosine 5'-monophosphate-activated protein kinase (AMPK) pathway. This influences immune cell infiltration, offering insights for ESCC treatment.

Area of Science:

  • Oncology
  • Immunotherapy
  • Molecular Biology

Background:

  • Esophageal squamous cell carcinoma (ESCC) remains a significant health challenge.
  • Understanding the mechanisms of immunotherapy response in ESCC is crucial for improving patient outcomes.
  • The serine threonine protein kinase 11 (STK11)/Adenosine 5 extquotesingle-monophosphate-activated protein kinase (AMPK) pathway is implicated in cellular metabolism and immune regulation.

Purpose of the Study:

  • To investigate the role of the STK11/AMPK signaling pathway in ESCC following immunotherapy.
  • To elucidate the relationship between this pathway and immune cell infiltration in ESCC patients.
  • To provide foundational data for optimizing clinical immunotherapy strategies for ESCC.

Main Methods:

  • Tissue specimens were collected from 100 patients who underwent surgery for ESCC (Group A) and 20 patients with recurrent/metastatic ESCC receiving second-line immunotherapy (Group B).
  • Real-time quantitative polymerase chain reaction (RT-qPCR) was employed to measure the expression of STK11, interferon-gamma (IFN-γ), interleukin-6 (IL-6), and vascular endothelial growth factor (VEGF).
  • Immunohistochemical staining assessed STK11 and AMPKα expression, while immunofluorescence staining evaluated T effector (Teff) cells, regulatory T (Treg) cells, and neutrophil infiltration.

Main Results:

  • Group A exhibited significantly lower STK11 and IFN-γ expression, and higher IL-6 and VEGF levels compared to Group B (P < 0.05).
  • STK11- and AMPKα-positive cells were markedly reduced in Group A versus Group B (P < 0.05).
  • Infiltration of Teff cells, Treg cells, and neutrophils was significantly lower in Group A compared to Group B (P < 0.05).

Conclusions:

  • Immunotherapy exerts a therapeutic effect in ESCC by modulating the STK11/AMPK pathway.
  • The STK11/AMPK pathway is closely associated with immune cell infiltration in the tumor microenvironment of ESCC.
  • These findings highlight the STK11/AMPK pathway as a potential therapeutic target for enhancing immunotherapy efficacy in ESCC.

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