AMPK activator AICAR in combination with anti-mouse IL10 mAb restores the functionality of intra-tumoral Tfh cells in the 4T1 mouse model.
Cell Immunol
; 382: 104639, 2022 12.
Article
em En
| MEDLINE
| ID: mdl-36375313
ABSTRACT
4T1 cell-mediated TNBC breast cell carcinoma is a highly malignant mice tumor model which resembles an advanced stage of breast cancer in humans. Tumor progression occurs depending on the intra-tumoral balance of pro- and anti- tumorigenic immune cells. Enhancement of T-cell-mediated anti-tumor immunity will be advantageous for inhibiting tumor progression and improving the efficacy of cancer therapy. This study is focused on alleviating suppressed anti-tumor immune response by improving CD4+ T follicular helper cell (Tfh) response in 4T1 mice. We employed anti-IL10 mAb along with metabolic drugs 2-deoxy-D-glucose (2DG) which inhibits the glycolytic pathway and Cpt1a inhibitor Etomoxir which inhibits FAO. AMPK activator AICAR with or without anti-IL10 mAb was also used to ameliorate metabolic stress and exhaustion faced by immune cells. Our results demonstrate that synergistic treatment with 2DG/Etomoxir + anti-IL10 mAb induced Tfh cell, memory B, and GC B cell response more potently compared to treatment with 2DG or Etomoxir treatment alone as observed in several LNs and tumor tissue of 4T1 mouse. However, AICAR + anti-IL10 mAb increased the frequency of intratumoral Tfh cells, simultaneously downregulated Tfr cells; and improved humoral response by stimulating upregulation of memory B, GC B, and plasmablasts in tumor-draining, axillary, and mesenteric LNs of 4T1 mouse.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteínas Quinases Ativadas por AMP
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Células T Auxiliares Foliculares
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Cell Immunol
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Índia