T cells drive negative feedback mechanisms in cancer associated fibroblasts, promoting expression of co-inhibitory ligands, CD73 and IL-27 in non-small cell lung cancer
| Autor: | Sandrine Prost, Ahsan R. Akram, Helen F Titmarsh, David A. Dorward, Layla Mathieson, Guilia Tagliavini, Kevin Dhaliwal, Richard A. O’Connor, Irene Young, Lilian Koppensteiner, Vishwani Chauhan, William A Wallace |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Interleukin-27
Stromal cell Lung Neoplasms T cell T-Lymphocytes Immunology T cells Major histocompatibility complex GPI-Linked Proteins Ligands crosstalk Feedback Non-small cell lung cancer Cancer-Associated Fibroblasts Carcinoma Non-Small-Cell Lung medicine Tumor Microenvironment Immunology and Allergy Cytotoxic T cell Humans Receptor 5'-Nucleotidase RC254-282 Original Research biology Chemistry Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC581-607 Immune checkpoint medicine.anatomical_structure Oncology Cancer cell Cancer research biology.protein Immunologic diseases. Allergy Research Article |
| Zdroj: | Oncoimmunology article-version (VoR) Version of Record O'Connor, R A, Chauhan, V, Mathieson, L, Titmarsh, H, Koppensteiner, L, Young, I, Tagliavini, G, Dorward, D, Prost, S, Dhaliwal, K, Wallace, W & Akram, A R 2021, ' T cells drive negative feedback mechanisms in Cancer Associated Fibroblasts, promoting expression of co-inhibitory ligands, CD73 and IL-27 in non-small cell lung cancer ', OncoImmunology . https://doi.org/10.1080/2162402X.2021.1940675 OncoImmunology, Vol 10, Iss 1 (2021) |
| ISSN: | 2162-402X 2162-4011 |
| Popis: | The success of immune checkpoint therapy shows tumour-reactive T cells can eliminate cancer cells but are restrained by immunosuppression within the tumour micro-environment (TME). Cancer Associated Fibroblasts (CAFs) are the dominant stromal cell in the TME and co-localise with T cells in non-small cell lung cancer. We demonstrate the bi-directional nature of CAF / T cell interactions; T cells promote expression of co-inhibitory ligands, MHC molecules and CD73 on CAFs, increasing their production of IL-6 and eliciting production of IL-27. In turn CAFs upregulate co-inhibitory receptors on T cells including the ectonucleotidase CD39 promoting development of an exhausted but highly cytotoxic phenotype. Our results highlight the bi-directional interaction between T cells and CAFs in promoting components of the immunosuppressive CD39, CD73 adenosine pathway and demonstrate IL-27 production can be induced in CAF by activated T cells. |
| Databáze: | OpenAIRE |
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