Anti-PD-(L)1 therapy of non-small cell lung cancer–A summary of clinical trials and current progresses

Mortezaee, Keywan; Majidpoor, Jamal

doi:10.1016/j.heliyon.2023.e14566

Cited by 5 publications

(2 citation statements)

References 110 publications

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“…10 In particular, patients without EGFR mutations comprise nearly 50% of the total LUAD population. Previous studies have reported that patients with LUAD EGFR‐negative tumors show a higher response to ICIs, 12 which may be largely determined by the complex tumor immune microenvironment (TME) in LUAD. 13 Thus, we explored in great depth an innovative “signature” based on the TME in EGFR‐negative LUAD to provide new insight into prognosis prediction and possible drug selection.…”

Section: Introductionmentioning

confidence: 99%

Exploring the immune landscape and drug prediction of an M2 tumor‐associated macrophage‐related gene signature in EGFR‐negative lung adenocarcinoma

Huang,

Zhang,

Duan

et al. 2024

Thoracic Cancer

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BackgroundImproving immunotherapy efficacy for EGFR‐negative lung adenocarcinoma (LUAD) patients remains a critical challenge, and the therapeutic effect of immunotherapy is largely determined by the tumor microenvironment (TME). Tumor‐associated macrophages (TAMs) are the top‐ranked immune infiltrating cells in the TME, and M2‐TAMs exert potent roles in tumor promotion and chemotherapy resistance. An M2‐TAM‐based prognostic signature was constructed by integrative analysis of single‐cell RNA‐seq (scRNA‐seq) and bulk RNA‐seq data to reveal the immune landscape and select drugs in EGFR‐negative LUAD.MethodsM2‐TAM‐based biomarkers were obtained from the intersection of bulk RNA‐seq data and scRNA‐seq data. After consensus clustering of EGFR‐negative LUAD into different clusters based on M2‐TAM‐based genes, we compared the prognosis, clinical features, estimate scores, immune infiltration, and checkpoint genes among the clusters. Next, we combined univariate Cox and LASSO regression analyses to establish an M2‐TAM‐based prognostic signature.ResultsCCL20, HLA‐DMA, HLA‐DRB5, KLF4, and TMSB4X were verified as prognostic M2‐like TAM‐related genes by univariate Cox and LASSO regression analyses. IPS and TMB analyses revealed that the high‐risk group responded better to common immunotherapy.ConclusionThe study shows the potential of the M2‐like TAM‐related gene signature in EGFR‐negative LUAD, explores the immune landscape based on M2‐like TAM‐related genes, and predict immunotherapy response of patients with EGFR‐negative LUAD, providing a new insight for individualized treatment.

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Section: Introductionmentioning

confidence: 99%

Exploring the immune landscape and drug prediction of an M2 tumor‐associated macrophage‐related gene signature in EGFR‐negative lung adenocarcinoma

Huang,

Zhang,

Duan

et al. 2024

Thoracic Cancer

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“…The higher expression of PD-1L on the surface of tumor cells allowed the patient’s lymphocytes to become anergic. Accordingly, PD-1/PD-1L axis-targeted immunotherapy is one of the most promising cancer treatments [ 7 , 8 ]. Obesity is an independent risk factor for lung cancer development and is associated with increased tumor growth and aggressiveness.…”

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confidence: 99%

Obesity and lung cancer – is programmed death ligand-1 (PD-1L) expression a connection?

Gałązka,

Czeczelewski,

Kucharczyk

et al. 2024

Arch Med Sci

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IntroductionIn this retrospective study, the authors evaluated whether obesity-induced immunomodulation impacts the expression of programmed death ligand-1 (PD-1L) in lung cancer cells.MethodsA retrospective cross-sectional study was performed. The study included 67 patients. The data did not have a normal distribution.ResultsFor women, using ANOVA test (p = 0.050) with post-hoc analysis, a statistically significant difference in expression was found between women with overweight and women with normal weight (p = 0.040).ConclusionsApart from the above, the authors did not find any statistically significant correlation between PD-1L expression on lung cancer cells and body mass index, either in the whole group or in histological subgroups.

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Toripalimab in combination with HBM4003, an anti-CTLA-4 heavy chain-only antibody, in advanced melanoma and other solid tumors: an open-label phase I trial

Tang,

Chen,

Jiang

et al. 2024

J Immunother Cancer

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BackgroundHBM4003 is a novel anti-CTLA-4 heavy chain-only antibody, designed to enhance Treg ablation and antibody-dependent cell-mediated cytotoxicity while ensuring a manageable safety profile. This phase I trial investigated the safety, pharmacokinetics, immunogenicity and preliminary efficacy of HBM4003 plus with anti-PD-1 antibody toripalimab in patients with advanced solid tumors, especially focusing on melanoma.MethodsThe multicenter, open-label phase I trial was divided into two parts: dose-escalation phase (part 1) and dose-expansion phase (part 2). In part 1, HBM4003 was administered at doses of 0.03, 0.1, 0.3 mg/kg in combination with toripalimab with fixed dosage of 240 mg every 3 weeks. The recommended phase II dose (RP2D) was used in the expansion phase. Primary endpoints were safety and RP2D in part 1 and objective response rate (ORR) in part 2. Biomarkers based on cytokines and multiplex immunofluorescence staining were explored.ResultsA total of 40 patients received study treatment, including 36 patients treated with RP2D of HBM4003 0.3 mg/kg plus toripalimab 240 mg every 3 week. 36 participants (90.0%) experienced at least one treatment-related adverse event (TRAE), of which 10 (25.0%) patients experienced grade ≥3 TRAEs and 5 (12.5%) experienced immune-mediated adverse events (irAEs) with maximum severity of grade 3. No grade 4 or 5 irAEs occurred. Efficacy analysis set included 32 melanoma patients treated with RP2D and with available post-baseline imaging data. The ORRs of anti-PD-1/PD-L1 treatment-naïve subgroup and anti-PD-1/PD-L1 treatment-failed subgroup were 33.3% and 5.9%, respectively. In mucosal melanoma, the ORR of the two subgroups were 40.0% and 10.0%, respectively. Baseline high Treg/CD4+ratio in the tumor serves as an independent predictive factor for the efficacy of immunotherapy.ConclusionsHBM4003 0.3 mg/kg plus toripalimab 240 mg every 3 week demonstrated manageable safety in solid tumors and no new safety signal. Limited data demonstrated promising antitumor activity, especially in PD-1 treatment-naïve mucosal melanoma.Trial registration numberNCT04727164.

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Anti-PD-(L)1 therapy of non-small cell lung cancer–A summary of clinical trials and current progresses

Cited by 5 publications

References 110 publications

Exploring the immune landscape and drug prediction of an M2 tumor‐associated macrophage‐related gene signature in EGFR‐negative lung adenocarcinoma

Exploring the immune landscape and drug prediction of an M2 tumor‐associated macrophage‐related gene signature in EGFR‐negative lung adenocarcinoma

Obesity and lung cancer – is programmed death ligand-1 (PD-1L) expression a connection?

Toripalimab in combination with HBM4003, an anti-CTLA-4 heavy chain-only antibody, in advanced melanoma and other solid tumors: an open-label phase I trial

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