Tumor cells and the extracellular matrix dictate the pro-tumoral profile of macrophages in CRC

Sara Coletta, Silvia Lonardi, Francesca Sensi, Edoardo D’angelo, Matteo Fassan, Salvatore Pucciarelli, Arianna Valzelli, Andrea Biccari, William Vermi, Chiara Della Bella, Annica Barizza, Mario Milco D’elios, Marina de Bernard, Marco Agostini, Gaia Codolo

Research output: Contribution to journalArticlepeer-review


Tumor-associated macrophages (TAMs) are major components of the tumor microenvi-ronment. In colorectal cancer (CRC), a strong infiltration of TAMs is accompanied by a decrease in effector T cells and an increase in the metastatic potential of CRC. We investigated the functional profile of TAMs infiltrating CRC tissue by immunohistochemistry, flow cytometry, ELISA, and qRT-PCR and their involvement in impairing the activation of effector T cells. In CRC biopsies, we evidenced a high percentage of macrophages with low expression of the antigen-presenting complex MHC-II and high expression of CD206. Monocytes co-cultured with tumor cells or a decellularized tumor matrix differentiated toward a pro-tumoral macrophage phenotype characterized by decreased expression of MHC-II and CD86 and increased expression of CD206 and an abundant release of pro-tumoral cytokines and chemokines. We demonstrated that the hampered expression of MHC-II in macrophages is due to the downregulation of the MHC-II transactivator CIITA and that this effect relies on increased expression of miRNAs targeting CIITA. As a result, macrophages become unable to present antigens to CD4 T lymphocytes. Our data suggest that the tumor microenvironment contributes to defining a pro-tumoral profile of macrophages infiltrating CRC tissue with impaired capacity to activate T cell effector functions.

Original languageEnglish
Article number5199
Pages (from-to)1-19
Number of pages19
Issue number20
Publication statusPublished - Oct 1 2021


  • Antigen presentation
  • Colorectal cancer
  • Extracellular matrix
  • Macrophages
  • MHC-II

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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