CD47 Expression Predicts Unfavorable Prognosis in Clear Cell Renal Cell Carcinoma after Curative Resection

Abstract

The role of CD47 expression as a ‘do not eat me’ signal that inhibits phagocytosis of tumor cells by macrophages is well established. Immune checkpoint therapy that targets CD47 has been successful in preclinical trials and is currently undergoing clinical investigation for various human malignancies. Here, the clinicopathological correlation with CD47 expression in clear cell renal cell carcinoma (ccRCC) was explored. CD47 expression was evaluated by immunohistochemical staining in tissue microarray sections of 235 ccRCC tissues. CD47 expression was observed in 28 (11.9%) of 235 ccRCC tissues and was significantly associated with higher WHO/ISUP grade (p = 0.001), frequent lymphovascular invasion (p = 0.036), frequent renal vein thrombus (p = 0.018), frequent sinus fat invasion (p = 0.004), frequent sarcomatous change (p = 0.001), higher pT stage (p = 0.002), higher pN stage (p = 0.002), higher pM stage (p < 0.001), and advanced American Joint Committee on Cancer stage (p = 0.002). In the survival analyses, positive CD47 expression was associated with cancer-specific survival (p = 0.003). However, positive CD47 expression was not associated with recurrence-free survival. In conclusion, CD47 expression was associated with adverse clinicopathological parameters and cancer-specific survival in patients with ccRCC.

Effect of CHST11, a novel biomarker, on the biological functionalities of clear cell renal cell carcinoma

“…In this context, NK cells are regarded as the primary bastion against hematogenous metastatic tumor cells, and reduced NK cell levels may favor an impending metastasis 30 . The decreased NK cell levels frequently coincide with the increased CD47 expression, which is related to a more invasive phenotype and a poor prognosis of ccRCC patients 34 . During ccRCC occurrence, immunoglobulins play a critical role in the evolution of neoplastic cells.…”

Immune Checkpoint Inhibitors in Renal Cell Carcinoma: Molecular Basis and Rationale for Their Use in Clinical Practice

“…CD47 on tumor cells may block macrophage phagocytosis by binding SIRP-α (signal regulatory protein α—an inhibitory receptor on phagocytes) [ 28 ]. Recently, CD47 expression has been associated with more aggressive phenotypes of clear cell renal cell carcinoma (ccRCC) and poorer patient prognosis [ 29 ]. NK cells destroy several tumor cell types, particularly those with decreased MHC I expression or that express ligands for NK-activating receptors.…”

Cellular and Molecular Players in the Tumor Microenvironment of Renal Cell Carcinoma

“…Upon binding to signal regulatory protein-α (SIRP-α, an inhibitory receptor on phagocytes), CD47 on tumor cells may block phagocytosis. Worse prognoses and more aggressive phenotypes of ccRCC have recently been linked to CD47 expression [ 71 , 72 ]. Multiple TAM phenotypes have been described, and different TAM subsets may coexist within tumors [ 73 ].…”