The CD47 “don't eat me signal” is highly expressed in human ovarian cancer

Abstract

Objectives The CD47 “don’t eat me” signal allows tumor immune evasion. We tested the association of CD47 expression with outcomes in EOC. Methods CD47 expression was examined within the TCGA database for ovarian carcinoma. For validation, IHC was performed on a TMA consisting of specimens from 265 patients with EOC. The medical records of the patients were also retrospectively reviewed to correlate demographic and survival data. Results CD47 was amplified in 15/316 (5%) ovarian serous cancers in TCGA. In the validation cohort, the majority of patients had stage III/IV disease (208/265, 78.4%). CD47 expression was seen in 210/265 (79.2%). Patients were categorized into CD47hi (129/265; 48.7%) versus CD47lo (136/265; 51.3%). Patients with CD47lo tumors were more likely to have a complete response to adjuvant therapy than CD47hi (65% vs 50%, p= 0.026). Although there was a trend towards an increase in median OS (37.64 vs 45.26 mos, p=0.92) in the CD47lo group compared with CD47hi, the difference was not significant. Conclusions CD47 is expressed at high frequency in EOC. Patients with CD47lo EOC had a better treatment response to standard therapy, and trended towards improved OS. This demonstrates that while CD47 may be an immunologic shield that may be considered for targeted therapies, it is likely that it operates in concert with other mechanisms of immune evasion. Future studies to evaluate CD47 expression with other known mechanisms of immune escape in the tumor microenvironment may help further define its role.

The CD47‐SIRPα signaling axis as an innate immune checkpoint in cancer

“…Furthermore, a number of patient studies have described the expression level of CD47 on cancer cells to be negatively associated with the response to therapy, including both chemotherapy and antibody therapy. This includes patients with either hematological or solid cancers, and low expression of CD47 on tumor cells was in many cases associated with a better prognosis and an improved survival of patients . It is known that cancer development and metastasis formation are primarily driven by so‐called tumor‐initiating cells and/or cancer stem cells (CSC), populations of cancer cells with strong capacity for self‐renewal, which are often also more resistant to many conventional cancer therapies .…”

“…Furthermore, a number of patient studies have described the expression level of CD47 on cancer cells to benegativelyassociatedwiththeresponsetotherapy,includingboth chemotherapyandantibodytherapy.Thisincludespatientswitheither hematologicalorsolidcancers,andlowexpressionofCD47ontumor cells was in many cases associated with a better prognosis 24,[57][58][59] andanimprovedsurvivalofpatients. 60 Of interest, more understanding about the regulation of CD47 expression on cancer cells at the molecular level has recently emerged. This was shown for instance by work of Zhang etal.…”

Combined prognostic value of the cancer stem cell markers CD47 and CD133 in esophageal squamous cell carcinoma

“…Cancer cells expressing CD47 transmit a “don't eat me” signal upon interacting with signal regulatory protein α on the surface of macrophages to deter phagocytosis . Previous studies have shown that CD47 is highly expressed on solid tumors such as in ovarian, breast, colon, bladder, glioblastoma, hepatocellular carcinoma and prostate cancer, and correlated with poorer prognoses in several cancer types including ESCC . Furthermore, anti‐CD47 antibody or CD47 blockade treatments have been demonstrated to enhance macrophage phagocytosis, reduce tumor burden, and increase patient survival in various tumor xenograft models …”

Advances in targeted therapy for malignant lymphoma

“…CD47/SIRPα CD47 is a new immune checkpoint that is expressed in normal cells and upregulated in various tumors. [396][397][398] Its ligand SIRPα is expressed on myeloid cells (monocytes, macrophages, and myeloid dendritic cells). CD47/SIRPα mainly regulates innate immune cell activity and sends out a "do not eat me" signal to escape the attack of innate immune cells.…”