Tumor associated CD70 expression is involved in promoting tumor migration and macrophage infiltration in GBM

Abstract

Tumor migration/metastasis and immunosuppression are major obstacles in effective cancer therapy. Incidentally, these 2 hurdles usually coexist inside tumors, therefore making therapy significantly more complicated, as both oncogenic mechanisms must be addressed for successful therapeutic intervention. Our recent report highlights that the tumor expression of a TNF family member, CD70, is correlated with poor survival for primary gliomas. In this study, we investigated how CD70 expression by GBM affects the characteristics of tumor cells and the tumor microenvironment. We found that the ablation of CD70 in primary GBM decreased CD44 and SOX2 gene expression, and inhibited tumor migration, growth and the ability to attract monocyte-derived M2 macrophages in vitro. In the tumor microenvironment, CD70 was associated with immune cell infiltrates, such as T cells; myeloid-derived suppressor cells; and monocytes/macrophages based on the RNA-sequencing profile. The CD163+ macrophages were far more abundant than T cells were. This overwhelming level of macrophages was identified only in GBM and not in low-grade gliomas and normal brain specimens, implying their tumor association. CD70 was detected only on tumor cells, not on macrophages, and was highly correlated with CD163 gene expression in primary GBM. Additionally, the co-expression of the CD70 and CD163 genes was found to correlate with decreased survival for patients with primary GBM. Together, these data suggest that CD70 expression is involved in promoting tumor aggressiveness and immunosuppression via tumor-associated macrophage recruitment/activation. Our current efforts to target this molecule using chimeric antigen receptor T cells hold great potential for treating patients with GBM.

OSgbm: An Online Consensus Survival Analysis Web Server for Glioblastoma

“…To determine the performance of this online tool, 53 previously published GBM prognostic factors collected as the procedure shown in Figure S1 and then they were evaluated in OSgbm (Table 2, Figure 1) (Sano et al, 1999;Hung and Howng, 2003;Heimberger et al, 2005;Aaberg-Jessen et al, 2009;Shirai et al, 2009;Pu et al, 2011;Cui et al, 2013;De Tayrac et al, 2013;Lee et al, 2013;Rosati et al, 2013;Wang et al, 2013;Wu et al, 2013;Bai et al, 2014;Han et al, 2014;Meng et al, 2014;Olmez et al, 2014;Zupancic et al, 2014;Maris et al, 2015;Moutal et al, 2015;Yan et al, 2015;Zhao et al, 2015;Chaurasia et al, 2016;Nduom et al, 2016;Steponaitis et al, 2016;Steponaitis et al, 2016;Zhang et al, 2016a;Zhang et al, 2016b;Deng et al, 2017;Dong et al, 2017;Ge et al, 2017;Han et al, 2017;Haynes et al, 2017;Huang et al, 2017;Li et al, 2017;Luo and Zhuang, 2017;Ma et al, 2017;Roy et al, 2017;Wu et al, 2017;Zhang et al, 2017;…”

Novel combinations to improve hematopoiesis in myelodysplastic syndrome

“…CD27, a costimulatory receptor of the TNF superfamily, is constitutively expressed on lymphocytes and hematopoietic stem/progenitor cells [44]. We found that CD27L is expressed on Lin − HLA-DR low CD11b + CD33 + MDSCs and the frequency of Lin − HLA-DR low CD11b + CD33 + CD27L + MDSCs is much higher in the BM than that in the peripheral blood of MDS patients [45].…”

Unveiling a CD70-positive subset of cancer-associated fibroblasts marked by pro-migratory activity and thriving regulatory T cell accumulation

“…Although we are the first to describe this effect by CD70-positive CAFs, CD70 overexpression on tumor cells has already been linked with migration in non-small cell lung cancer, melanoma and glioblastoma. [28][29][30] In the latter, knockdown of the CD70 gene resulted in a decrease in genes associated with tumor epithelial-mesenchymal transition (EMT) such as CD44 and SOX2. Also in CRC, overexpression of CD44 has been shown to drive EMT changes.…”