Combination of pembrolizumab and 125I attenuates the aggressiveness of non‑small cell lung cancer

Abstract

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-associated mortality. Therapies targeting programmed cell death 1 ligand 1 (PD1L1) have promising effects on NSCLC. However, resistance to targeted therapy has become the main problem and the underling molecular mechanism remains unclear. In the present study, the expression of PD1L1 in NSCLC was determined and the association with clinicopathological characteristics was analyzed. A combination therapy was also constructed, including pembrolizumab (Pem) and iodine-125 ( 125 I), which represented an efficient strategy for the treatment of NSCLC. The expression of PD1L1 was upregulated in NSCLC tissues and positively correlated with the Ki-67 index, pathological subtypes and risk stages. A higher level of PD1L1 expression was associated with poorer survival in patients with NSCLC, which could be used as a prognostic indicator. When NSCLC cells were cultured in the presence of Pem and 125 I seeds, the combination treatment significantly abrogated the tumor proliferation and aggressiveness through the inhibition of matrix metalloproteinase-2 and -9 secretion. Flow cytometry analysis revealed pembrolizumab combined with 125 I contributed to a higher rate of apoptosis and cell cycle arrest, indicating that the combination treatment improved the resistance to immunotherapy. Furthermore, the associated molecular mechanism was the dysregulation of ADAM metallopeptidase domain 17. The findings from the present study revealed that PD1L1 could be used as a predictive biomarker, and the application of combination treatment of pembrolizumab and 125 I showed promising effects on NSCLC.Abbreviations: PD1L1, programmed cell death 1 ligand 1; ADAM17, ADAM metallopeptidase domain 17; RT-qPCR, reverse transcriptase-quantitative polymerase chain reaction; PI, propidium iodide; MMP, matrix metalloproteinase; FCM, flow cytometry Key words: non-small cell lung cancer, programmed cell death 1 ligand 1, iodine-125, targeted therapy

OLFML2B is a Prognostic Biomarker in Lung Adenocarcinoma and Squamous Cell Carcinoma

“…Notably, the in ltrating immune cells consist of various lymphocytes that can attack the tumor cells or help the tumor cells survive the host immune system [39]. Previously, we reported that PD-L1/PD1 were highly expressed in NSCLC and combination of pembrolizumab and 125I attenuates the aggressiveness of this disorder [40]. Both PD-L1/PD1 and OLFML2B could construct the immunosuppressive microenvironment.…”

125I brachytherapy as consolidative local therapy for patients with synchonous oligometastatic non-small cell lung cancer without progression after first-line chemotherapy plus PD-1 inhibitors treatment：A retrospective observational study

“…Third, Treating each site can reduce cancer genetic diversity, delaying progression due to emergence of treatment-resistant clonogens and further seeding from the metastatic sites(Turajlic and Swanton 2016). Fourth, 125 I seed brachytherapy may bolster antitumor immune-mediated effect by promoting cancer antigen presentation and lymphocytic tumor in ltration(Wang et al 2020). Finally,we used chemotherapy plus immunotherapy before 125 I seed implantation, such design can select for patients with an intrinsically more indolent disease trajectory or tumors more sensitivity to systemic therapy because any patients whose cancer had progressed during systemic therapy would have been excluded from the trail.…”