Diverging prognostic effects of CD155 and CD73 expressions in locally advanced triple-negative breast cancer

• Published in: Frontiers in oncology Vol. 13; p. 1165257
• Main Authors: Cabioglu, Neslihan, Bayram, Aysel, Emiroglu, Selman, Onder, Semen, Karatay, Huseyin, Oner, Gizem, Tukenmez, Mustafa, Muslumanoglu, Mahmut, Igci, Abdullah, Aydiner, Adnan, Saip, Pinar, Yavuz, Ekrem, Ozmen, Vahit
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 13.07.2023
• Subjects: CD155; CD73; chemotherapy response; Oncology; prognosis; triple-negative breast cancer; CD73; triple-negative breast cancer; chemotherapy response; prognosis; CD155
• ISSN: 2234-943X; 2234-943X
• DOI: 10.3389/fonc.2023.1165257

Immune checkpoint inhibition, combined with novel biomarkers, may provide alternative pathways for treating chemotherapy-resistant triple-negative breast cancer (TNBC). This study investigates the expression of new immune checkpoint receptors, including CD155 and CD73, which play a role in T and natural killer (NK) cell activities, in patients with residual TNBC after neoadjuvant chemotherapy (NAC). The expression of biomarkers was immunohistochemically examined by staining archival tissue from surgical specimens (n = 53) using specific monoclonal antibodies for PD-L1, CD155, and CD73. Of those, 59.2% (29/49) were found to be positive (>1%) for PD-L1 on the tumour and tumour-infiltrating lymphocytes (TILs), while CD155 (30/53, 56.6%) and CD73 (24/53, 45.3%) were detected on tumours. Tumour expressions of CD155 and CD73 significantly correlated with PD-L1 expression on the tumour (p = 0.004 for CD155, p = 0.001 for CD73). Patients with CD155 positivity ≥10% were more likely to have a poor chemotherapy response, as evidenced by higher MDACC Residual Cancer Burden Index scores and Class II/III than those without CD155 expression (100% vs 82.6%, p = 0.03). At a median follow-up time of 80 months (range, 24-239), patients with high CD73 expression showed improved 10-year disease-free survival (DFS) and disease-specific survival (DSS) rates compared to those with low CD73 expression. In contrast, patients with CD155 (≥10%) expression exhibited a decreasing trend in 10-year DFS and DSS compared to cases with lower expression, although statistical significance was not reached. However, patients with coexpression of CD155 (≥10%) and low CD73 were significantly more likely to have decreased 10-year DFS and DSS rates compared to others (p = 0.005). These results demonstrate high expression of CD73 and CD155 in patients with residual tumours following NAC. CD155 expression was associated with a poor response to NAC and poor prognosis in this chemotherapy-resistant TNBC cohort, supporting the use of additional immune checkpoint receptor inhibitor therapy. Interestingly, the interaction between CD155 and CD73 at lower levels resulted in a worse outcome than either marker alone, which calls for further investigation in future studies.