Associations of immune cell homing gene signatures and infiltrates of lymphocyte subsets in human melanomas: discordance with CD163+ myeloid cell infiltrates

Journal of Translational Medicine

Victor H. Engelhard¹  Stefan Bekiranov²  Gulsun Erdag³  Katie M. Leick³  Craig L. Slingluff⁴  Minyoung Kwak⁴ 

[1] Carter Center for Immunology Research, University of Virginia, Charlottesville, VA, USA;Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA, USA;Department of Surgery, University of Virginia, P.O. Box 800709, 22908-0709, Charlottesville, VA, USA;Department of Surgery, University of Virginia, P.O. Box 800709, 22908-0709, Charlottesville, VA, USA;Carter Center for Immunology Research, University of Virginia, Charlottesville, VA, USA;

关键词: Homing;    Chemokines;    Integrins;    Immune cells;    Lymphocytes;    Gene expression;    Melanoma;   

DOI  :  10.1186/s12967-021-03044-5

来源: Springer

【 摘 要 】

BackgroundImmune cells in the tumor microenvironment have prognostic value. In preclinical models, recruitment and infiltration of these cells depends on immune cell homing (ICH) genes such as chemokines, cell adhesion molecules, and integrins. We hypothesized ICH ligands CXCL9-11 and CCL2-5 would be associated with intratumoral T-cells, while CXCL13 would be more associated with B-cell infiltrates.MethodsSamples of human melanoma were submitted for gene expression analysis and immune cells identified by immunohistochemistry. Associations between the two were evaluated with unsupervised hierarchical clustering using correlation matrices from Spearman rank tests. Univariate analysis performed Mann–Whitney tests.ResultsFor 119 melanoma specimens, analysis of 78 ICH genes revealed association among genes with nonspecific increase of multiple immune cell subsets: CD45+, CD8+ and CD4+ T-cells, CD20+ B-cells, CD138+ plasma cells, and CD56+ NK-cells. ICH genes most associated with these infiltrates included ITGB2, ITGAL, CCL19, CXCL13, plus receptor/ligand pairs CXCL9 and CXCL10 with CXCR3; CCL4 and CCL5 with CCR5. This top ICH gene expression signature was also associated with genes representing immune-activation and effector function. In contrast, CD163+ M2-macrophages was weakly associated with a different ICH gene signature.ConclusionThese data do not support our hypothesis that each immune cell subset is uniquely associated with specific ICH genes. Instead, a larger set of ICH genes identifies melanomas with concordant infiltration of B-cell and T-cell lineages, while CD163+ M2-macrophage infiltration suggesting alternate mechanisms for their recruitment. Future studies should explore the extent ICH gene signature contributes to tertiary lymphoid structures or cross-talk between homing pathways.

【 授权许可】

CC BY