Predictive value of CD73 expression for the efficacy of immune checkpoint inhibitors in NSCLC

Abstract

Background CD73 induces the dephosphorylation of adenosine monophosphate converting it to adenosine, enabling malignancies to escape from immune surveillance. Although CD73 overexpression has been reported to be a poor prognostic factor in several malignancies including non‐small cell lung cancer (NSCLC), its predictive relevance in NSCLC patients receiving immune checkpoint inhibitors is unknown. The present research was conducted to investigate the prognostic significance of CD73 expression in NSCLC patients receiving immune checkpoint inhibitors (ICIs). Methods We screened 91 patients with advanced or recurrent NSCLC who received immune checkpoint inhibitors. CD73 expression was evaluated immunohistochemically using tissue specimens obtained just before treatment with ICIs. Results Analysis of progression‐free survival (PFS) and overall survival (OS) in relation to several levels of CD73 expression (1%, 10%, 30%, and 50%) showed that both tended to be more favorable as expression of CD73 increased. PFS and OS were longer for patients in whom at least 50% of the tumor cells expressed CD73 than for those in whom <50% of the tumor cells did so. In patients who were positive for EGFR mutation, immune checkpoint inhibitors were significantly more effective in those with high CD73 expression, whereas CD73 expression did not significantly affect the efficacy in patients with EGFR mutation‐negative NSCLC. Furthermore, CD73 expression was predictive factor for the PFS independent of PD‐L1 expression in patients with EGFR mutation. Conclusions High CD73 expression may predict a favorable response to ICIs in NSCLC patients, especially those harboring EGFR mutations. Key points Significant findings of the study: In patients who were positive for EGFR mutation, immune checkpoint inhibitors (ICIs) were significantly more effective in those with high CD73 expression, whereas CD73 expression did not significantly affect the efficacy in patients with EGFR mutation‐negative NSCLC. What this study adds: High CD73 expression may predict a favorable response to immune checkpoint inhibitors in NSCLC patients, especially those harboring EGFR mutations.

Targeting Immunometabolism Mediated by CD73 Pathway in EGFR-Mutated Non-small Cell Lung Cancer: A New Hope for Overcoming Immune Resistance

“…By contrast, Ishii et al retrospectively showed that high CD73 expression correlated with favorable clinical efficacy of immunotherapy in patients with EGFR-mutated NSCLC who have developed resistance to EGFR-TKIs, although this study had some limitations such as the limited number of patients analyzed (63).…”

“…CD73 is endogenously expressed on endothelial cells, epithelial cells, and some immune subsets, and its expression has also been observed in several cancer types, including melanoma, colon, breast, ovarian, and lung cancer (19). Notably, the main drivers of CD73 expression within TME include hypoxia, TGF-β, type I IFN, IL-1, and prostaglandin (63).…”

Multiplex immune protein profiling of fine‐needle aspirates from patients with non‐small‐cell lung cancer reveals signatures associated with PD‐L1 expression and tumor stage

“…We here for the first time show that PEA can be used to decipher immune and tumor signaling in minute FNA material also from NSCLC lesions. Some of these immune signaling components are reported to be of relevance to response to ICIs [ 13 , 23 , 25 , 27 , 28 , 36 ]. Thus, our study points at a possible path to overcome certain of the challenges for interventional oncology as previously outlined by Schoenberg et al .…”

“…Signaling in tumor cells per se or its microenvironment is an important driver for both intrinsic and acquired therapy resistance to both targeted therapy as well as to ICIs [ 13 , 23 , 25 , 27 , 28 , 36 ]. Here, we report analysis of pairwise consecutive FNA samples from six patients and compared expression of > 160 different proteins.…”

CD73 Severed as a Potential Prognostic Marker and Promote Lung Cancer Cells Migration via Enhancing EMT Progression

“…First, for enzymatic function, CD73 is a rate-limiting enzyme in the production of extracellular adenosine. High concentration of CD73-generated adenosine in microenvironment is an anti-inflammatory agent, which prevents excess inflammatory reactions and has been shown to be involved in tumor immunity escapes ( Chen et al, 2020 ; Ishii et al, 2020 ). Thus, CD73-adenosine axis have been considered as a further immune checkpoint to exploit target treatment.…”