CD70: A Potential Target in Breast Cancer?

Abstract

CD70 is a co-stimulatory molecule involved in the immune response and also in cancer development and progression. Recent studies show that high CD70 expression in cancer cells may inhibit the anti-tumor response. Furthermore, CD70 expression has been reported as a predictive marker of resistance to chemotherapy in ovarian cancers. Some in vitro studies have shown that CD70 expression is epigenetically down-regulated through hypermethylation of its promoter during tumoral progression. This study evaluated the level of CD70 expression in surgical samples of breast invasive tumors and determined its correlation with CD70 promoter methylation.Twenty “luminal A” and 20 “basal-like” frozen samples from early breast tumors were retrospectively selected. CD70 expression was evaluated by quantitative real-time PCR. Total DNA was bisulfite-treated, and methylation levels of 5 consecutive CG sites present in the proximal region (-464, -421) of the promoter were assessed by pyrosequencing analysis. Statistical analyses were performed using the Mann-Whitney test.The median relative CD70 expression level was 0.37 and was significantly higher in the basal-like group (0.78 [0.24-31.7]) compared to the luminal A group (0.25 [0.03-1.83], p=0.0001). The median methylation level was 61%, with no significant difference between the basal-like (63%) and luminal A (58%) groups. No correlation was found between CD70 expression and CD70 methylation level.In this study, higher CD70 expression was observed in the basal-like group, but this expression was not related to promoter methylation. The higher expression in the poor-prognosis subgroup of patients makes CD70 a potential target for emerging anti-CD70 therapies.

CD70: An emerging target in cancer immunotherapy

“…Likewise, epigenetic aberrations of the CD70 promoter region in breast cancer cells have also been demonstrated to affect CD70 expression (Petrau et al, 2014;S. E. Yu et al, 2010).…”

“…High rates of CD70 expression are particularly found in lymphomas, renal cell carcinoma (RCC), nasopharyngeal carcinoma, as well as in Epstein-Barr virus-induced carcinomas (Table 1) (Agathanggelou et al, 1995;Boursalian et al, 2009;Israel et al, 2005). In B cell lymphoma, RCC and breast cancer, CD70 expression is associated with poor prognosis (Bertrand et al, 2013;Jilaveanu et al, 2012;Petrau et al, 2014). Interestingly, next to its expression on primary tumor-biopsies, stable CD70 expression is also found on patient-derived metastatic tissue in up to 100% of cases (Jacobs et al, 2015;Law et al, 2006).…”

Clinical relevance of CD70 expression in resected pancreatic cancer: prognostic value and therapeutic potential

“…Recently, aberrant CD70 expression in cancer cells has been observed in several tumor types, including RCC [7,21], lymphocytic leukemia [11,19], ovarian carcinoma [8] [16], and breast cancer [14,15]. These ndings suggest that blocking CD70-related signals could be an appropriate therapeutic strategy for some tumors [9,19].…”

The expansion of targetable biomarkers for CAR T cell therapy

“…Expression of CD70 is limited to diffuse large B-cell and follicular lymphomas, as well as Hodgkin’s lymphoma, multiple myeloma, and EBV-associated malignancies [ 51 – 55 ]. Additionally, CD70 is also expressed on other malignancies such as glioma [ 56 – 59 ], breast cancer [ 60 , 61 ], renal cell carcinoma [ 51 , 62 – 64 ], ovarian cancer [ 65 – 67 ], and pancreatic cancer [ 65 , 68 ]. Targeting this antigen is feasible as CD70/CD27 signaling is not essential for the development of a functional immune system as CD27 −/− mice recover from infection in a similar time frame as CD27 WT mice [ 69 , 70 ].…”