Tumor mutation burden and immunological, genomic, and clinicopathological factors as biomarkers for checkpoint inhibitor treatment of patients with non-small-cell lung cancer

Ozaki, Yuki; Muto, Satoshi; Takagi, Hironori; Watanabe, Masayuki; Inoue, Takuya; Fukuhara, Mitsuro; Yamaura, Takumi; Okabe, Naoyuki; Matsumura, Yuki; Hasegawa, T.; Ohsugi, Jun; Hoshino, Mika; Shio, Yutaka; Tanaka, Daisuke; Nanamiya, Hideaki; Imai, Jun‐ichi; Isogai, Takao; Watanabe, Shinya; Suzuki, Hiroyuki

doi:10.1007/s00262-019-02446-1

Cited by 38 publications

(35 citation statements)

References 38 publications

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“…Previous studies have indicated that NTRK3 affects multiple signaling pathways, including the MAPK and PI3K pathways, which further promote cell differentiation and affect tumor progression (Jin et al, 2010;Ozaki et al, 2020). Similarly, some effects on these pathways correlate with NTRK3 mutations.…”

Section: Discussionmentioning

confidence: 97%

“…Although ICIs are widely used in cancer treatment, predictive biomarkers for prognosis of patients to ICIs are not well established. Regardless, PD-L1 expression, TMB, NAL and microsatellite instability (MSI) status are promising biomarkers for ICIs, even though their predictive ability remains limited (Ozaki et al, 2020). Therefore, biomarkers that are more accurate and clinically useful than these biomarkers for predicting the efficacy of ICI treatment are needed.…”

Section: Discussionmentioning

confidence: 99%

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Prognosis of Lung Adenocarcinoma Patients With NTRK3 Mutations to Immune Checkpoint Inhibitors

Niu¹,

Lin²,

Luo³

et al. 2020

Front. Pharmacol.

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Background: Immune checkpoint inhibitors (ICIs) are an important treatment modality that must be considered for patients with lung adenocarcinoma (LUAD). However, ICIs are effective only in some of these patients. Therefore, identifying biomarkers that accurately predict the prognosis of patients with LUAD treated with ICIs can help maximize their therapeutic benefits. This study aimed to identify a new potential predictor to better select and optimally benefit LUAD patients.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Prognosis of Lung Adenocarcinoma Patients With NTRK3 Mutations to Immune Checkpoint Inhibitors

Niu¹,

Lin²,

Luo³

et al. 2020

Front. Pharmacol.

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show abstract

“…For those without recurrence or death by the end of follow-up, survival end points were censored at the date of last follow-up. 23 A Cox proportionalhazard model was constructed for OS in multivariate analysis. Backward selection was used to adjust potential confounding covariate.…”

Section: Discussionmentioning

confidence: 99%

<p>Influence of Programmed Death Ligand-1-Gene Polymorphism rs822336 on the Prognosis and Safety of Postoperative Patients with NSCLC Who Received Platinum-Based Adjuvant Chemotherapy</p>

Zhao¹,

Zhang²,

Chen

et al. 2020

CMAR

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This study was done to investigate the influence of PDL1-gene polymorphism on the prognosis and safety of postoperative patients with non-small cell lung cancer (NSCLC) who had received platinum-based adjuvant chemotherapy. Methods: A total of 289 postoperative patients with NSCLC who had received platinumbased adjuvant chemotherapy from January 2012 to June 2019 participated in this study. Recurrence status and adverse reactions were documented during adjuvant chemotherapy. Overall survival (OS) data were obtained through telephone follow-up. DNA extracted from hematologic specimens was genotyped for PDL1-gene polymorphism. Associations between genotype status and prognosis were assessed using Kaplan-Meier survival analysis, and multivariate adjustment was performed using Cox regression analysis. Results: Median disease-free survival of the 289 patients with NSCLC was 3.3 years and median OS 4.9 years. With regard to the PDL1 gene polymorphism, only rs822336 was of clinical significance in the subsequent analysis. The minor-allele frequency of rs822336 was 0.21, and distribution of the three genotypes was in accordance with the Hardy-Weinberg equilibrium (P=0.807). Survival analysis according to genotype status suggested that median disease-free survival of patients with GG and GC/CC genotypes was 2.8 and 4.1 years, respectively (P=0.01). Median OS of patients with GG and GC/CC genotypes was 4.1 and 5.4 years, respectively (P=0.008). However, the safety analysis failed to find a significant association between the polymorphism and adverse reactions. Interestingly, expression analysis of RNA extracted from peripheral blood mononuclear cells indicated that PDL1-mRNA expression of patients with the GG genotype was significantly higher than for the GC/CC genotype (P<0.001). Conclusion: The prognosis of postoperative patients with NSCLC who have received platinum-based adjuvant chemotherapy may be influenced by the rs822336 polymorphism through mediation of the mRNA expression of PDL1.

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“…[ 59 ] Another study also reports that TMB is associated with the EGFR -wild lung cancers. [ 60 ] Interestingly, a study reports that durvalumab improves the objective response (OR) of EGFR / ALK -mutated NSCLC patients with ≥25% of PD-L1 expression. [ 61 ] Furthermore, a combination of atezolizumab with tyrosine kinase inhibitor (TKI) is shown to be effective on TKI-invalid patients with EGFR mutation.…”

Section: Biomarkersmentioning

confidence: 99%

Biomarkers or factors for predicting the efficacy and adverse effects of immune checkpoint inhibitors in lung cancer: achievements and prospective

Shi

Zhao²

2020

Chinese Medical Journal

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Immune checkpoint inhibitors (ICIs) are widely used in lung cancer therapy due to their effectiveness and minimal side effects. However, only a few lung cancer patients benefit from ICI therapy, driving the need to develop alternative biomarkers. Programmed death-ligand 1 (PD-L1) molecules expressed in tumor cells and immune cells play a key role in the immune checkpoint pathway. Therefore, PD-L1 expression is a prognostic biomarker in evaluating the effectiveness of programmed death-1 (PD-1)/PD-L1 inhibitors. Nevertheless, adverse predictive outcomes suggest that other factors are implicated in the response. In this review, we present a detailed introduction of existing biomarkers concerning tumor abnormality and host immunity. PD-L1 expression, tumor mutation burden, neoantigens, specific gene mutations, circulating tumor DNA, human leukocyte antigen class I, tumor microenvironment, peripheral inflammatory cells, and microbiome are discussed in detail. To sum up, this review provides information on the current application and future prospects of ICI biomarkers.

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Tumor mutation burden and immunological, genomic, and clinicopathological factors as biomarkers for checkpoint inhibitor treatment of patients with non-small-cell lung cancer

Abstract: Tumor mutation burden and immunological, genomic, and clinicopathological factors as biomarkers for checkpoint inhibitor treatment of patients with non-small-cell lung cancer.

Cited by 38 publications

References 38 publications

Prognosis of Lung Adenocarcinoma Patients With NTRK3 Mutations to Immune Checkpoint Inhibitors

Prognosis of Lung Adenocarcinoma Patients With NTRK3 Mutations to Immune Checkpoint Inhibitors

<p>Influence of Programmed Death Ligand-1-Gene Polymorphism rs822336 on the Prognosis and Safety of Postoperative Patients with NSCLC Who Received Platinum-Based Adjuvant Chemotherapy</p>

Biomarkers or factors for predicting the efficacy and adverse effects of immune checkpoint inhibitors in lung cancer: achievements and prospective

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