Targeting crosstalk of STAT3 between tumor-associated M2 macrophages and Tregs in colorectal cancer.
Lili HuangYu ZhaoMengying ShanSitong WangJianhua ChenZhuqing LiuQing XuPublished in: Cancer biology & therapy (2023)
A comprehensive analysis of the molecular mechanism underlying colorectal tumor evaluated the development of colorectal cancer (CRC) and proposed targeting small molecular inhibitors. Nonetheless, the adoptive resistance of these therapies remains a challenge with respect to achieving an effective clinical response. Thus, identifying the molecular mechanisms guiding CRC growth is essential. The results of The Cancer Genome Atlas (TCGA) dataset analysis demonstrated a critical role of signal transducer and activator of transcription 3 (STAT3) pathway in tumor immune suppression via modulation of the recruitment of Treg cells and M2 type tumor-associated macrophages. The in vivo experiments elucidate that targeting STAT3 pathways markedly reduce the proportions of TAMs and Tregs by inhibiting tumor progression. These findings revealed crosstalk between Treg cells and M2 macrophages, proving a potential therapeutic strategy for CRC therapy. Combinatorial treatment with STAT3 inhibitor and programmed death 1 (PD-1) antibody therapy effectively prevents CRC tumor growth in a mouse model with high anti-tumor immunity. In summary, targeting STAT3 disrupts the interaction between Treg cells and M2 macrophages and improves the anti-tumor response in CRC, thereby offering a promising strategy to treat patients with CRC.
Keyphrases
- induced apoptosis
- cell cycle arrest
- cell proliferation
- mouse model
- cancer therapy
- stem cells
- endoplasmic reticulum stress
- cell therapy
- oxidative stress
- cell death
- transcription factor
- squamous cell carcinoma
- single cell
- poor prognosis
- dna methylation
- inflammatory response
- genome wide
- young adults
- nuclear factor
- toll like receptor
- squamous cell