Biomaterial Database

Tumor cell-derived IL-10 promotes cell-autonomous growth and immune escape in diffuse large B-cell lymphoma. 2021

Kristin Stirm, and Peter Leary, and Katrin Bertram, and Nicolás Gonzalo Núñez, and Daria Wüst, and Christophe Boudesco, and Els Verhoeyen, and Thorsten Zenz, and Burkhard Becher, and Thomas Menter, and Alexandar Tzankov, and Anne Müller

Institute of Molecular Cancer Research, University of Zurich, Zurich, Switzerland.

Diffuse large B-cell lymphoma (DLBCL) is an aggressive malignancy arising from germinal center or post-germinal center B-cells that retain many of the properties of normal B-cells. Here we show that a subset of DLBCL express the cytokine IL-10 and its receptor. The genetic ablation of IL-10 receptor signaling abrogates the autocrine STAT3 phosphorylation triggered by tumor cell-intrinsic IL-10 expression and impairs growth of DLBCL cell lines in subcutaneous and orthotopic xenotransplantation models. Furthermore, we demonstrate using an immunocompetent Myc-driven model of DLBCL that neutralization of IL-10 signaling reduces tumor growth, which can be attributed to reduced Treg infiltration, stronger intratumoral effector T-cell responses, and restored tumor-specific MHCII expression. The effects of IL-10R neutralization were phenocopied by the genetic ablation of IL-10 signaling in the Treg compartment and could be reversed by MHCII blockade. The BTK inhibitor ibrutinib effectively blocked tumor cell-intrinsic IL-10 expression and tumor growth in this Myc-driven model. Tumors from patients with high IL-10RA expression are infiltrated by higher numbers of Tregs than IL-10RAlow patients. Finally, we show in 16 cases of DLBCL derived from transplant patients on immunosuppressive therapy that IL-10RA expression is less common in this cohort, and Treg infiltration is not observed.

UI	MeSH Term	Description	Entries
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D016403	Lymphoma, Large B-Cell, Diffuse	Malignant lymphoma composed of large B lymphoid cells whose nuclear size can exceed normal macrophage nuclei, or more than twice the size of a normal lymphocyte. The pattern is predominantly diffuse. Most of these lymphomas represent the malignant counterpart of B-lymphocytes at midstage in the process of differentiation.	Diffuse Large B-Cell Lymphoma,Diffuse, Large B-Cell, Lymphoma,Histiocytic Lymphoma, Diffuse,Lymphoma, Histiocytic, Diffuse,Diffuse Large-Cell Lymphoma,Histiocytic Lymphoma,Large Lymphoid Lymphoma, Diffuse,Large-Cell Lymphoma, Diffuse,Lymphoma, Diffuse Large-Cell,Lymphoma, Histiocytic,Lymphoma, Large Cell, Diffuse,Lymphoma, Large Lymphoid, Diffuse,Lymphoma, Large-Cell, Diffuse,Diffuse Histiocytic Lymphoma,Diffuse Histiocytic Lymphomas,Diffuse Large B Cell Lymphoma,Diffuse Large Cell Lymphoma,Diffuse Large-Cell Lymphomas,Histiocytic Lymphomas,Large Cell Lymphoma, Diffuse,Lymphoma, Diffuse Histiocytic,Lymphoma, Diffuse Large Cell
D016753	Interleukin-10	A cytokine produced by a variety of cell types, including T-LYMPHOCYTES; MONOCYTES; DENDRITIC CELLS; and EPITHELIAL CELLS that exerts a variety of effects on immunoregulation and INFLAMMATION. Interleukin-10 combines with itself to form a homodimeric molecule that is the biologically active form of the protein.	IL-10,CSIF-10,Cytokine Synthesis Inhibitory Factor,IL10,Interleukin 10
D045744	Cell Line, Tumor	A cell line derived from cultured tumor cells.	Tumor Cell Line,Cell Lines, Tumor,Line, Tumor Cell,Lines, Tumor Cell,Tumor Cell Lines
D049109	Cell Proliferation	All of the processes involved in increasing CELL NUMBER including CELL DIVISION.	Cell Growth in Number,Cellular Proliferation,Cell Multiplication,Cell Number Growth,Growth, Cell Number,Multiplication, Cell,Number Growth, Cell,Proliferation, Cell,Proliferation, Cellular
D018858	Germinal Center	The activated center of a lymphoid follicle in secondary lymphoid tissue where B-LYMPHOCYTES are stimulated by antigens and helper T cells (T-LYMPHOCYTES, HELPER-INDUCER) are stimulated to generate memory cells.	Center, Germinal,Centers, Germinal,Germinal Centers