CD73: A potential biomarker for anti-PD-1 therapy

Beavis, Paul A.; Slaney, Clare Y.; Milenkovski, Nicole; Henderson, Melissa A.; Loi, Sherene; Stagg, John; Kershaw, Michael H.; Darcy, Phillip K.

doi:10.1080/2162402x.2015.1046675

Cited by 33 publications

(18 citation statements)

References 9 publications

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“…One advantage of targeting the adenosine pathway is the safety profile of adenosine receptor inhibitors, established in phase I-III clinical trials in Parkinson disease (48). A recent study suggested CD73 as a biomarker for anti-PD-1 therapy (49) and CD73 and A2AR blockade can further enhance the therapeutic activity of immune checkpoint inhibitors (18,19,49,50). Despite the lack of a critical role for lymphocytes in A2BRi antimetastatic activity, the A2BRi PSB1115 improved the antimetastatic activity of anti-PD-1 and anti-CTLA-4 mAbs in two different models of metastasis (one experimental and one spontaneous), and this may be associated with an additive direct effect of A2BRi PSB1115 on cancer cell metastasis and alleviating immune suppression by immune checkpoint inhibitors.…”

Section: Discussionmentioning

confidence: 99%

Adenosine 2B Receptor Expression on Cancer Cells Promotes Metastasis

et al. 2016

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Adenosine plays an important role in inflammation and tumor development, progression, and responses to therapy. We show that an adenosine 2B receptor inhibitor (A2BRi) decreases both experimental and spontaneous metastasis and combines with chemotherapy or immune checkpoint inhibitors in mouse models of melanoma and triple-negative breast cancer (TNBC) metastasis. Decreased metastasis upon A2BR inhibition is independent of host A2BR and lymphocytes and myeloid cells. Knockdown of A2BR on mouse and human cancer cells reduces their metastasis in vivo and decreases their viability and colony-forming ability, while transiently delaying cell-cycle arrest in vitro. The prometastatic activity of adenosine is partly tumor A2BR dependent and independent of host A2BR expression. In humans, TNBC cell lines express higher A2BR than luminal and Her2 þ breast cancer cell lines, and high expression of A2BR is associated with worse prognosis in TNBC. Collectively, high A2BR on mouse and human tumors promotes cancer metastasis and is an ideal candidate for therapeutic intervention. Cancer Res; 76(15); 4372-82. Ó2016 AACR.

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Section: Discussionmentioning

confidence: 99%

Adenosine 2B Receptor Expression on Cancer Cells Promotes Metastasis

et al. 2016

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“…As a consequence, high expression of the enzyme CD73 is associated with a poor prognosis in various cancer types (164–166). This enzyme is also a potential biomarker for anti-PD-1 therapy, since CD73 expression limits anti-PD-1 efficacy (161, 167). Indeed, both combined treatment with anti-CD73 and anti-CTLA-4 or anti-PD-1 enhanced the antitumor activity in colon (MC38), prostate (RM-1), and metastatic breast cancer (4T1.2) models (168).…”

Section: Combinations That Increase Tumor Killing (Step 7)mentioning

confidence: 99%

Combination Approaches with Immune-Checkpoint Blockade in Cancer Therapy

2016

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In healthy individuals, immune-checkpoint molecules prevent autoimmune responses and limit immune cell-mediated tissue damage. Tumors frequently exploit these molecules to evade eradication by the immune system. Over the past years, immune-checkpoint blockade of cytotoxic T lymphocyte antigen-4 and programed death-1 emerged as promising strategies to activate antitumor cytotoxic T cell responses. Although complete regression and long-term survival is achieved in some patients, not all patients respond. This review describes promising, novel combination approaches involving immune-checkpoint blockade in the context of the cancer-immunity cycle, aimed at increasing response rates to the single treatments. Specifically, we discuss combinations that promote antigen release and presentation, that further amplify T cell activation, that inhibit trafficking of regulatory T cells or MSDCs, that stimulate intratumoral T cell infiltration, that increase cancer recognition by T cells, and that stimulate tumor killing.

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“…CD73 is considered as a potential biomarker for PD-1 therapy (15). Targeted blockade of CD73 can enhance the therapeutic activity of anti-PD-1 and anti-CTLA-4 monoclonal antibodies and may thus potentiate therapeutic strategies targeting immune checkpoint inhibitors in general (40).…”

Section: Who 2010 Classification ------------------------------------mentioning

confidence: 99%

“…We hypothesized that CD73 is expressed on the cytomembrane of GI-NENs with high malignant potential. CD73 is also considered as a potential biomarker for anti-programmed death-1 (PD-1) therapy (15).…”

Section: Introductionmentioning

confidence: 99%

Immunohistochemical CD73 expression status in gastrointestinal neuroendocrine neoplasms: A retrospective study of 136ï¿½patients

et al. 2017

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Abstract. The WHO 2010 classification divides gastrointestinal neuroendocrine neoplasms (GI-NENs) into neuroendocrine tumor (NET) G1, NET G2, neuroendocrine carcinoma (NEC) and mixed adenoendocrine carcinoma (MANEC) groups. A total of 136 cases of GI-NENs diagnosed at our hospitals as gastrointestinal carcinoids, endocrine cell carcinomas and NENs over the last 11 years, using the WHO 2010 classification were assessed. Among the 136 cases, 88.2% (120/136) were classified into the NET group (NET G1/G2) and 11.8% (16/136) were classified into the NEC group (NEC/MANEC). The incidences of lymphatic and venous invasions were higher in the NEC group compared with in the NET group (P<0.0001 and P=0.0021, respectively). The immunohistochemical staining of cluster of differentiation 73 (CD73) was evaluated in GI-NENs. CD73 is a potentially useful molecule in tumor immunity. In general, CD73 on the tumor cell membrane converts adenosine monophosphate to adenosine, which restrains the production of interferon-γ and cytocidal activity. Although the association between stem cells of pancreatic NENs and CD73 has been reported, few studies have reported on CD73 expression in GI-NENs. Immunohistochemical CD73 expression on the cytomembrane of neuroendocrine cells was detected in 27.2% (37/136) of the GI-NENs. The positive ratio of CD73 was significantly higher in the NEC group compared with in the NET group (P=0.0015). CD73 is also considered as a potential biomarker of anti-programmed death-1 (PD-1) therapy. The expression of programmed death-ligand 1 (PD-L1) on the cytomembrane of GI-NENs was assessed. The positive ratio of PD-L1 was higher in the NEC group compared with in the NET group (P=0.0011). Furthermore, CD73 expression status was significantly correlated with PD-L1 expression (P<0.0001). These results indicate that CD73 may be an interesting candidate for a biomarker for certain prognostic factors and therapeutics concerning PD-1 therapy.

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CD73: A potential biomarker for anti-PD-1 therapy

Cited by 33 publications

References 9 publications

Adenosine 2B Receptor Expression on Cancer Cells Promotes Metastasis

Adenosine 2B Receptor Expression on Cancer Cells Promotes Metastasis

Combination Approaches with Immune-Checkpoint Blockade in Cancer Therapy

Immunohistochemical CD73 expression status in gastrointestinal neuroendocrine neoplasms: A retrospective study of 136ï¿½patients

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