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Updated: Aug 11, 2025

A Robust Discovery Platform for the Identification of Novel Mediators of Melanoma Metastasis
07:41

A Robust Discovery Platform for the Identification of Novel Mediators of Melanoma Metastasis

Published on: March 8, 2022

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Carbon ion irradiation induces DNA damage in melanoma and optimizes the tumor microenvironment based on the

Yanan Guo1, Rong Shen1, Fang Wang1,2

  • 1School of Basic Medical Sciences, Lanzhou University, Lanzhou, 73000, Gansu, China.

Journal of Cancer Research and Clinical Oncology
|February 6, 2023
PubMed
Abstract

Insights

Carbon ion radiotherapy (CIRT) enhances anti-tumor immunity in melanoma by increasing DNA damage and activating the cGAS/STING pathway. CIRT combined with PD-L1 inhibitors shows significant melanoma growth inhibition.

Area of Science:

  • Oncology
  • Immunology
  • Radiotherapy

Background:

  • The Cyclic GMP-AMP synthase/stimulator of interferon genes (cGAS/STING) pathway is critical for anti-tumor immunity.
  • Understanding the role of cGAS/STING in melanoma's tumor immune microenvironment after carbon ion radiotherapy (CIRT) is essential.

Purpose of the Study:

  • To investigate the effects of CIRT on the melanoma tumor immune microenvironment.
  • To elucidate the underlying mechanisms involving the cGAS/STING pathway and DNA damage response.

Main Methods:

  • Utilized C57BL/6 mouse melanoma models to compare CIRT, X-ray, PD-L1 inhibitor, and combination therapies.
  • Assessed tumor-infiltrating lymphocytes (TILs) using mass cytometry.
  • Investigated DNA damage response (DDR) and cGAS/STING pathway activation via immunofluorescence and molecular measurements.

Main Results:

  • CIRT induced greater DNA damage and cGAS/STING activation than X-ray, slowing melanoma growth.
  • CIRT significantly boosted TILs (NK, CD4+, CD8+ T cells) and immune checkpoint expression (PD-1, LAG-3, TIM-3).
  • Combination therapy of CIRT and PD-L1 inhibitor further enhanced anti-tumor effects by increasing T cell and NK cell infiltration.

Conclusions:

  • CIRT effectively enhances anti-tumor immunity in melanoma by inducing DNA damage and activating the cGAS/STING pathway.
  • CIRT shows potential as a synergistic treatment with radiotherapy and radioimmunotherapy for melanoma.
  • Findings offer insights for designing clinical strategies for melanoma treatment.
Keywords:
Carbon ionImmunotherapyPD-L1 inhibitorSTINGX-raycGAS

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