SBRT combined with PD-1/PD-L1 inhibitors in NSCLC treatment: a focus on the mechanisms, advances, and future challenges

Abstract

Immune checkpoint inhibitors targeting programmed cell death 1 (PD-1), programmed cell death ligand-1 (PD-L1), and others have shown potent clinical efficacy and have revolutionized the treatment protocols of a broad spectrum of tumor types, especially non-small-cell lung cancer (NSCLC). Despite the substantial optimism of treatment with PD-1/PD-L1 inhibitors, there is still a large proportion of patients with advanced NSCLC who are resistant to the inhibitors. Preclinical and clinical trials have demonstrated that radiotherapy can induce a systemic antitumor immune response and have a great potential to sensitize refractory "cold" tumors to immunotherapy. Stereotactic body radiation therapy (SBRT), as a novel radiotherapy modality that delivers higher doses to smaller target lesions, has shown favorable antitumor effects with significantly improved local and distant control as well as better survival benefits in various solid tumors. Notably, research has revealed that SBRT is superior to conventional radiotherapy, possibly because of its more powerful immune activation effects. Thus, PD-1/PD-L1 inhibitors combined with SBRT instead of conventional radiotherapy might be more promising to fight against NSCLC, further achieving more favorable survival outcomes. In this review, we focus on the underlying mechanisms and recent advances of SBRT combined with PD-1/PD-L1 inhibitors with an emphasis on some future challenges and directions that warrant further investigation.

The construction, expression, and enhanced anti-tumor activity of YM101: a bispecific antibody simultaneously targeting TGF-β and PD-L1

“…A series of clinical studies showed that anti-PD-1/ PD-L1 antibodies had robust and durable anti-cancer activities across several solid and hematologic cancers, such as lung cancer [7][8][9], renal cell cancer [10], melanoma [11], hepatocellular carcinoma [12], as well as lymphoma [13][14][15]. Besides, synergistic anti-tumor responses have been observed in combination of anti-PD1/PD-L1 with PARP inhibition [16] or radiotherapy [17]. Although considerable success has been made in clinic trials, just a subset of patients could benefit from anti-PD-1/PD-L1 treatment, and the overall response rate is relatively low [18,19].…”

Comprehensive Analysis of Acetylation-Related lncRNAs and Identified AC099850.3 as Prognostic Biomarker in Non-Small Cell Lung Cancer

“…ere are many ways to treat lung cancer, for example, conventional cisplatin-based chemotherapy for NSCLC gives moderate efficacy [11]; Afatinib can be used as a firstline treatment for patients with EGFR-positive mutations in NSCLC [12]; PD-L1 inhibitors joined with SBRT instead of conventional radiotherapy might fight against NSCLC, further achieving more favorable survival outcomes [13]. However, in the process of long-term treatment, primary and secondary drug resistance can occur in all patients who receive targeted therapy, leading to treatment failure [14,15].…”

Modified Glasgow Prognostic Score is predictive of prognosis for non-small cell lung cancer patients treated with stereotactic body radiation therapy: a retrospective study

“…A series of studies have confirmed the short-term safety of combining SBRT and immunotherapy [ 39–42 ]. However, there is no clear consensus available on the optimal radiation dose and schedule for combining SBRT with immunotherapy [ 43 ]. We hypothesize that use of immunotherapy will reduce locoregional and distant recurrence with a resulting improvement in OS following SBRT for NSCLC.…”