Journal Article Ahead of print
PubMed: 42423754 DOI: 10.1007/s10911-026-09613-y
COX-2- and IDO-associated immunomodulatory functions of stage II carcinoma-associated fibroblasts in breast cancer.
J Mammary Gland Biol Neoplasia
Authors: Ladan Langroudi, Zuhair M Hasan, Masoud Soleimani, Seyed Mahmoud Hashemi
Affiliations
- Department of Immunology, School of Medicine, Kerman University of Medical Sciences, Kerman, Iran.
- Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Jalal AleAhmad Highway, Nasr Bridge, Tehran, Iran.
- Department of Hematology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
- Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Abstract
The immune response against cancer is influenced by the tumor stroma. Carcinoma-associated fibroblasts (CAFs), a significant part of the stroma, are important modulators of the tumour microenvironment (TME). The current study examined the immunomodulatory properties of CAFs isolated from a stage II mouse model of mammary invasive ductal cancer. Based on the expression of surface markers, we described Stage II CAFs and assessed their effects on cytokine release, nitric oxide (NO) generation, and splenocyte proliferation in direct co-culture systems. Class II MHC molecules (I-Ad/I-Ed), FAP-1, CD29, CD90, and CD105 were all expressed by isolated CAFs, indicating the possibility of direct immunological contact. In direct co-culture, CAFs demonstrated two distinct functions: their conditioned medium (CM) had immunosuppressive effects, whereas direct cell interactions promoted splenocyte growth. Additionally, CAFs changed the cytokine milieu, particularly by secreting high levels of TGF-β and PGE₂, and dramatically reduced splenocyte NO generation. COX-2, IDO, and MMP2 were significantly upregulated in CAFs, according to gene expression data. Our results emphasize the potential of Stage II CAFs as a therapeutic target in breast cancer by demonstrating their complex immunomodulatory character, which includes the ability to both stimulate and repress immune responses through cellular contact and soluble factors.
MeSH
Cytokines, Cells, Genes, Breast Neoplasms, Neoplasms, Breast, Immunity, Fibroblasts