The C-C chemokine receptor type 5 (CCR5) expressed on immune cells supports inflammatory responses by directing cells to the inflammation site. CCR5 is also a major coreceptor for macrophage tropic human immunodeficiency viruses (R5-HIV-1) and its variants can confer protection from HIV infection, making it an ideal candidate to target for therapy. We developed a stepwise protocol that differentiates induced pluripotent stem cells (iPSCs) from individuals homozygous for the CCR5Δ32 variant and healthy volunteers into myeloid lineage induced monocytes (iMono) and macrophages (iMac). By characterizing iMono and iMac against their primary counterparts, we demonstrated that CCR5Δ32 homozygous cells are endowed with similar pluripotent potential for self-renewal and differentiation as iPSC lines generated from non-variant individuals while also showing resistance to HIV infection. In conclusion, these cells are a platform to investigate CCR5 pathophysiology in HIV-positive and negative individuals and to help develop novel therapies.

Colony stimulating factor 1 receptor (CSF-1R) is a single channel III transmembrane receptor tyrosine kinase (RTK) and plays an important role in immune regulation and the development of various cancer types. The expression of CSF-1R in colon adenocarcinoma (COAD) and its prognostic value remain incompletely understood. Therefore, we aim to explore the prognostic value of CSF-1R in COAD and its relationship with tumor immunity.
CSF-1R expression in a COAD cohort containing 103 patients was examined using immunohistochemistry (IHC). The relationship between CSF-1R expression and clinicopathological parameters and prognosis was evaluated. Dual immunofluorescence staining was conducted to determine the localization of CSF-1R in COAD tissues. Univariate and multivariate Cox regression analysis were performed to evaluate independent prognostic factors. Transcriptomic profiles of CSF-1Rhigh and CSF-1Rlow tumor-associated macrophages (TAMs) were investigated. Gene enrichment analysis was used to explore the signal pathways related to CSF-1R. In addition, the relationship between CSF-1R in tumor microenvironment (TME) and tumor immunity was also studied.
IHC analysis showed that CSF-1R was overexpressed in COAD, and higher expression was associated with shorter overall survival (OS). Immunofluorescence staining showed that CSF-1R was co-localized with macrophage marker CD68. Univariate and multivariate Cox regression analysis showed that CSF-1R was an independent prognostic factor for COAD. The results of gene enrichment analysis showed that CSF-1R was involved in tumor immune response and regulation of TME. In addition, CSF-1R was significantly correlated with TME, immune cell infiltration, TMB, MSI, Neoantigen, and immune checkpoint molecules.
CSF-1R can serve as an independent prognostic factor of COAD and promising immunotherapeutic target of COAD.
Copyright © 2022 Wang, Zhang, Hu and Qian.