Search

Background: Immune checkpoint inhibitors (ICIs), either as monotherapy or in combination with chemotherapy, have improved the therapeutic outcome for non-small cell lung cancer (NSCLC). However, the efficacy of combination therapies, such as programmed cell death 1(PD-1)/its ligand (PD-L1) and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) inhibitors, in targeting different pathways remains unclear. We performed a meta-analysis to determine whether the addition of a CTLA-4 inhibitor to PD-1/PD-L1 therapy improves the efficacy of PD-1/PD-L1 monotherapy in NSCLC. Methods: We systematically searched various electronic databases for suitable trials. Only randomized controlled trials (RCTs) comparing the clinical efficacy of PD-1/PD-L1 with and without CTLA-4 were included in the analyses. The meta-analysis software RevMan 5.3 was used for statistical analyses. Results: A total of seven RCTs were retrieved. The results suggested that the combination of CTLA-4 and PD-1/PDL-1 inhibitors did not show enhanced efficacy over PD1/PDL-1 inhibitor monotherapy as determined by overall survival (OS) (HR = 0.98, 95% CI = 0.84-1.14, p = 0.79), progression-free survival (PFS) (HR = 0.92, 95% CI = 0.81-1.06, p = 0.25), and objective response rate (ORR) (HR = 1.08, 95% CI = 0.96-1.21, p = 0.19). Furthermore, the combination immunotherapy was associated increased toxicity as evidenced by increased incidence of any type adverse events (AEs) (RR = 1.06, 95% CI = 1.00-1.13, p = 0.03), grade ≥3 immune-mediated AEs (RR = 1.58, 95% CI = 1.36-1.82, p < 0.05), and treatment discontinuation (RR = 1.83, 95% CI = 1.46--2.28, p < 0.05). Conclusion: Combining anti-CTLA-4 with anti-PD-1/PD-L1 therapy did not improve the therapeutic efficacy, and was associated with greater toxicity than anti-PD-1/PD-L1 monotherapy in patients with advanced NSCLC. Further investigation of the combination immunotherapy in specific subsets of patients is warranted to identify and define the patient-specific benefits of this combination. [ABSTRACT FROM AUTHOR]

The genus Neocinnamomumis considered to be one of themost enigmatic groups in Lauraceae, mainlydistributedintropical andsubtropical regionsofSoutheastAsia. The genus contains valuable oilseed andmedicinal tree species. However, there are few studies on the genus Neocinnamomum at present, and its interspecific relationship is still unclear. In order to explore the genetic structure and evolutionary characteristics of the Neocinnamomum chloroplast genome and to resolve the species relationships within the genus, comparative genomic and phylogenetic analyses were performed on the whole chloroplast genome sequences of 51 samples representing seven Neocinnamomum taxa. The whole Neocinnamomumchloroplast genome size ranged from150,753-150,956 bp, with a GC content of 38.8%-38.9%. A total of 128 genes were annotated within the Neocinnamomumchloroplast genome, including 84 protein coding genes, 8 rRNA genes, and 36 tRNA genes. Between 71-82 SSRs were detected, among which A/T base repeatswere themost common. The chloroplast genome contained a total of 31preferredcodons. Threehighly variableregions, trnN-GUU-ndhF, petA-psbJ, and ccsA-ndhD, were identified with Pi values > 0.004. Based on the whole chloroplast genome phylogenetic tree, the phylogenetic relationships among the seven Neocinnamomum taxa were determined. N. delavayi and N. fargesii were the most closely related species, and N. lecomtei was identified as the most basal taxon. In this study, the characteristics and sequence variation of the chloroplast genomes of seven Neocinnamomum taxa were revealed, and the genetic relationship among the species was clarified. The results of this study will provide a reference for subsequent molecular marker development and phylogenetic research of Neocinnamomum. [ABSTRACT FROM AUTHOR]