Human T cells interacting with HNSCC‐derived mesenchymal stromal cells acquire tissue‐resident memory like properties. Issue 10 (2nd June 2020)

• Record Type: Journal Article
• Authors: Mazzoni, Alessio; Maggi, Laura; Montaini, Gianni; Ramazzotti, Matteo; Capone, Manuela; Vanni, Anna; Locatello, Luca Giovanni; Barra, Giusi; De Palma, Raffaele; Gallo, Oreste; Cosmi, Lorenzo; Liotta, Francesco; Annunziato, Francesco
• Is Part Of: European journal of immunology. Volume 50:Issue 10(2020)
• Page Start: 1571
• Page End: 1579
• Publication Date: 2020-06-02
• Subjects: Tissue‐resident memory -- T cells -- HNSCC -- Stromal cells -- VCAM1; Immunology -- Periodicals; 616.079
• DOI: 10.1002/eji.202048544
• Languages: English
• ISSNs: 0014-2980

Abstract

Abstract: Tissue‐resident memory (Trm) cells are specialized components of both CD4+ and CD8+ T cell subsets that persist in peripheral nonlymphoid tissues following infections and provide fast response in case of a secondary invasion by the same pathogen. Trm cells express the surface markers CD69, CD103, and the immune checkpoint molecule PD‐1. Trm cells develop not only in the context of infections but also in tumors, where they can provide a line of defense as suggested by the positive correlation between the frequency of tumor‐infiltrating Trm cells and patients' survival. Trm cells persistence in peripheral tissues depends on their adaptation to the local microenvironment and the presence of survival factors, mainly IL‐7, IL‐15, and Notch ligands. However, the cell sources of these factors are largely unknown, especially in the context of tumors. Here, we show that head–neck squamous cell carcinoma (HNSCC) is enriched in CD4+ and CD8+ T cells with a Trm phenotype. Moreover, we show that mesenchymal stromal cells that accumulate in HNSCC are a source of survival factors and allow proper expression of Trm‐typical markers in a VCAM1‐dependent manner. Abstract : T‐cell‐derived IFN‐γ and TNF‐α act on mesenchymal stromal cells in head–neck squamous cell carcinoma microenvironment and promote the upregulation of PDL1, DLL1, VCAM1, and the secretion of IL‐7 and IL‐15. These mechanisms concur to the expression of tissue‐residency markers CD103 and CD69 by CD4 and CD8 T cells and to their survival.