Immunologic and clinical implications of CD73 expression in non-small cell lung cancer (NSCLC).

Park, Lee Chun; Rhee, Kyunghoon; Kim, Won Bin; Cho, Anderson; Song, Jong‐Keol; Anker, Jonathan F.; Oh, Michael S.; Bais, Preeti; Namburi, Sandeep; Chuang, Jeffrey H.; Chae, Young Kwang

doi:10.1200/jco.2018.36.15_suppl.12050

Cited by 18 publications

(28 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These mice also benefit from increased chemotherapy sensitivity (36,71) and reduced angiogenesis (71,72). In line with these studies, many human tumors overexpress CD73 and associates with poor prognosis (36,(73)(74)(75)(76)(77)(78). CD73 is also linked to drug resistance, epithelial-to-mesenchymal transition (EMT), and cancer cell proliferation and stemness (76,(79)(80)(81)(82)(83)(84).…”

Section: Cd73 and Adenosine Receptor Activity Promotes Immunosuppressionmentioning

confidence: 77%

“…Whether CD73 expression associates with dMMR/MSI-H in GI tumors and its blockade would further increase immunotherapy efficacy in these tumors is unknown. In NSCLC studies, tumor mutational burden and neoantigen burden does not associate with CD73 high or low expression (74). Taking advantage of strong associations of CD73 with molecular and genetic alterations (e.g., KRAS mutation and EGFR alterations) may benefit GI cancers.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

CD73's Potential as an Immunotherapy Target in Gastrointestinal Cancers

et al. 2020

View full text Add to dashboard Cite

CD73, a cell surface 5 ′ nucleotidase that generates adenosine, has emerged as an attractive therapeutic target for reprogramming cancer cells and the tumor microenvironment to dampen antitumor immune cell evasion. Decades of studies have paved the way for these findings, starting with the discovery of adenosine signaling, particularly adenosine A2A receptor (A2AR) signaling, as a potent suppressor of tissue-devastating immune cell responses, and evolving with studies focusing on CD73 in breast cancer, melanoma, and non-small cell lung cancer. Gastrointestinal (GI) cancers are a major cause of cancer-related deaths. Evidence is mounting that shows promise for improving patient outcomes through incorporation of immunomodulatory strategies as single agents or in combination with current treatment options. Recently, several immune checkpoint inhibitors received FDA approval for use in GI cancers; however, clinical benefit is limited. Investigating molecular mechanisms promoting immunosuppression, such as CD73, in GI cancers can aid in current efforts to extend the efficacy of immunotherapy to more patients. In this review, we discuss current clinical and basic research studies on CD73 in GI cancers, including gastric, liver, pancreatic, and colorectal cancer, with special focus on the potential of CD73 as an immunotherapy target in these cancers. We also present a summary of current clinical studies targeting CD73 and/or A2AR and combination of these therapies with immune checkpoint inhibitors.

show abstract

Section: Cd73 and Adenosine Receptor Activity Promotes Immunosuppressionmentioning

confidence: 77%

Section: Discussionmentioning

confidence: 99%

CD73's Potential as an Immunotherapy Target in Gastrointestinal Cancers

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Changes in expression of membranous immunomodulatory molecules in the TME and release of immunosuppressive soluble factors, such as TGF-β, IL-10 and adenosine (ADO) [47,48], play a crucial role in tumor progression.…”

Section: Cell Surface Molecules and Selected Soluble Factorsmentioning

confidence: 99%

“…Several reports have reported that the tumor microenvironment (TME) [31][32][33][34][35][36], tumor immunogenicity [37][38][39], tumor-specific mutations, copy number variants [40,41] and abundances of specific intestinal bacteria can [42] affect the efficacy of ICIs. Multiple studies have demonstrated that EGFR mutations in NSCLC are more likely to correlate with an immunosuppressive TME [41,[43][44][45][46][47][48], the tumor mutation burden (TMB) [43,49], and expression of PD-L1 [41,[50][51][52][53]. In addition, EGFR-TKIs may modulate the immune response by regulating TME.…”

Section: Introductionmentioning

confidence: 99%

“…Immunosuppressive effects of EGFR mutations have also been described in recent years. Several studies have reported that EGFR mutations can modulate possible factors related to the status of the TME, such as tumorinfiltrating lymphocytes (TILs) [41,43,65], Tregs [45,66], MDSCs [47,67] tumor-associated macrophages (TAMs) [47], immunoregulatory cytokines [47,48] and exosomes [68]. These preclinical and clinical findings suggest that the TME of NSCLC patients with EGFR mutations may be unique, differing from patients with wildtype EGFR, and that EGFR mutations may impact the antitumor immune response by affecting the TME (Fig.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Role of the dynamic tumor microenvironment in controversies regarding immune checkpoint inhibitors for the treatment of non-small cell lung cancer (NSCLC) with EGFR mutations

et al. 2019

View full text Add to dashboard Cite

Immunotherapy has been incorporated into the first- and second-line treatment strategies for non-small cell lung cancer (NSCLC), profoundly ushering in a new treatment landscape. However, both adaptive signaling and oncogenic (epidermal growth factor receptor (EGFR)-driven) signaling may induce PD-L1 upregulation in NSCLC. Nevertheless, the superiority of immune checkpoint inhibitors (ICIs) in advanced EGFR-mutant NSCLC is only moderate. ICIs appear to be well tolerated, but clinical activity for some advanced EGFR-mutant NSCLC patients has only been observed in a small proportion of trials. Hence, there are still several open questions about PD-L1 axis inhibitors in patients with NSCLC whose tumors harbor EGFR mutations, such as the effect of EGFR tyrosine kinase inhibitors (TKIs) or EGFR mutations in the tumor microenvironment (TME). Finding the answers to these questions requires ongoing trials and preclinical studies to identify the mechanisms explaining this possible increased susceptibility and to identify prognostic molecular and clinical markers that may predict benefits with PD-1 axis inhibition in this specific NSCLC subpopulation. The presence of multiple mechanisms, including dynamic immune TME profiles, changes in PD-L1 expression and low tumor mutational burdens, may explain the conflicting data regarding the correlation between PD-L1 axis inhibitors and EGFR mutation status. We conducted a review of this currently controversial topic in an attempt to aid in the decision-making process.

show abstract

The efficacy and possible mechanisms of immune checkpoint inhibitors in treating non‐small cell lung cancer patients with epidermal growth factor receptor mutation

Diao

Huang

et al. 2021

Cancer Communications

View full text Add to dashboard Cite

Over the past few years, immune checkpoint inhibitors (ICIs) have greatly improved the survival for patients with non-small cell lung cancer (NSCLC) without driver mutations. Compared with wild-type tumors, tumors with epidermal growth factor receptor (EGFR) mutations show more heterogeneity in the expression level of programmed cell death-ligand 1 (PD-L1), tumor mutational burden (TMB), and other immune microenvironment characteristics. Whether ICIs are suitable for NSCLC patients with EGFR mutations is still worth exploring. In previous studies, no significantly improved benefits were observed with immunotherapy monotherapy in NSCLC patients with EGFR mutation. Here, we summarized and analyzed data from the clinical trials of ICIs or combined therapy in NSCLC patients with EGFR mutations. We also focused on the mecha-

show abstract

Immunologic and clinical implications of CD73 expression in non-small cell lung cancer (NSCLC).

Cited by 18 publications

References 0 publications

CD73's Potential as an Immunotherapy Target in Gastrointestinal Cancers

CD73's Potential as an Immunotherapy Target in Gastrointestinal Cancers

Role of the dynamic tumor microenvironment in controversies regarding immune checkpoint inhibitors for the treatment of non-small cell lung cancer (NSCLC) with EGFR mutations

The efficacy and possible mechanisms of immune checkpoint inhibitors in treating non‐small cell lung cancer patients with epidermal growth factor receptor mutation

Contact Info

Product

Resources

About