Prognostic value of CD73 expression in resected colorectal cancer liver metastasis

Abstract

Immune checkpoint blockade has not yet been effective in patients with mismatch repair proficient metastatic colorectal cancer. Targeting immunosuppressive metabolic pathways is being explored as a new immunotherapeutic approach. We assessed whether CD73, the rate limiting enzyme that catalyzes the degradation of extracellular AMP into immunosuppressive adenosine, could be an immunological determinant of colorectal liver metastases (CRLMs). By immunofluorescence on tissue microarrays, intratumoral CD73 expression (tCD73) was analyzed in 391 CRLMs resected in 215 patients, and soluble CD73 (sCD73) was measured by ELISA in the pre-operative serum of 193 patients. High tCD73 was associated with worse pathological features, such as multiple and larger CRLMs, and poorer pathologic response to pre-operative chemotherapy. The median time to recurrence and diseasespecific survival after CRLM resection was significantly shorter in patients with high tCD73 (11.0 and 46.4 months, respectively) compared with low tCD73 (19.0 and 61.5 months, respectively). tCD73 was strongly associated with patient outcomes independently of clinicopathological variables. sCD73 did not correlate with tCD73. Patients with high levels of sCD73 also had shorter disease-specific survival. Our results suggested that CD73 in CRLMs may be prognostically informative and may help select patients more likely to respond to adenosine pathway blocking agents.

Immunogenic cell death and its therapeutic or prognostic potential in high-grade glioma

“…Furthermore, both enzymes regulate the magnitude of the purinergic reaction surrounding the immune cells. High expression of CD73 is therefore associated with low levels of lymphocytes in the TME and poor prognosis in for example colorectal, prostate, and triple-negative breast cancer [ 44 – 47 ]. Of note, CD73 is regulated by HIF-1alpha and therefore more abundant in a hypoxic microenvironment [ 48 ].…”

Serum CD73 is a prognostic factor in patients with metastatic melanoma and is associated with response to anti-PD-1 therapy

“…[27][28][29] Recently published data from patients with colorectal cancer liver metastases show that high levels of soluble CD73 expression are associated with shorter survival. 21 These results indicate that soluble CD73 may serve as a non-invasive blood-based biomarker of cancer outcome. Yet, it is unclear whether soluble CD73 is a clinically useful biomarker of prognosis and response to immunotherapy in patients with melanoma.…”

High expression of CD73 contributes to poor prognosis of clear-cell renal cell carcinoma by promoting cell proliferation and migration

“…Overexpression of CD73 has been demonstrated to be correlated with poor clinical outcomes in diverse cancers ( 9 - 13 , 20 , 21 ). In a cohort of 902 patients with gastric cancer, CD73 expression was more intensive in gastric cancer tissues and patients with high levels of CD73 had significantly poorer OS and DFS ( 22 ).…”

“…The role of CD73 in different cancer cells has been also widely studied. It’s indicated that high expression of CD73 is associated with poor prognosis in various cancers, including melanoma ( 9 ), papillary thyroid carcinoma ( 10 ), hepatocellular carcinoma ( 11 ), triple-negative breast cancer ( 12 ), and colorectal cancer ( 13 ). For RCC, a recently study also showed that high CD73 expression portended significantly worse disease-free survival (DFS) and overall survival (OS), indicating that CD73 might be a potent therapeutic target for RCC patients ( 14 ).…”