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

Abstract

Background Immune 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. Methods Samples 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. Results For 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. Conclusion These 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.

Glomerular immune injury promotes anti-tumor activity

“…Principal component analysis (PCA) showed a clear separation between the two groups (Figure 3E). In addition, BMCs from NTN- injected mice demonstrated strong immune cell homing gene signatures 23 as shown by upregulation of Ccr4, Cxcr3, Ccl5, Cxcr5, Ccr1, Ccl2, Ccl4, and Ccr5 (Figure 3F). Moreover, we observed alterations in the gene signatures of both myeloid lineage markers and lymphoid lineage markers following NTN (Figure 3G-H).…”

Classification of colon adenocarcinoma based on immunological characterizations: Implications for prognosis and immunotherapy

“…In comparison, the majority of cases in IS2 were MSS/MSI-L, which showed the lowest relative proportion of immune cells, which was potentially due to the low checkpoint-related gene expression levels. It has been reported that a high CCL4/CCL5/CXCL9/CXCL10 expression is strongly associated with CD8 + T-cell infiltration and T-cell activation (48)(49)(50)(51). Moreover, CXCL9, CXCL10, and CXCL11/CXCR3 axis play a central role in immune activation (52,53).…”

Data-driven analysis to identify prognostic immune-related biomarkers in BRAF mutated cutaneous melanoma microenvironment

“…The combination of anti-PD1 and anti-CSF1 receptor (CSF1R) antibodies induced the regression of melanoma in-driven transplanted mice ( Neubert et al, 2018 ). ITGB2 is associated with immune infiltration of multiple immune cell subsets, such as CD45, CD8, CD4T cells, CD20B cells and so on ( Kwak et al, 2021 ). Although there was no direct evidence for the association between TYROBP and melanoma, given the important association between these hub genes and immune infiltration, we regard them as potential therapeutic targets for patients with BRAF mutations.…”