Potential biomarkers for immunotherapy in non-small-cell lung cancer

Wang, Xing; Qiao, Zi-yun; Aramini, Beatrice; Dong, Lin; Li, Xiaolong; Jiang, Fan

doi:10.1007/s10555-022-10074-y

Cited by 6 publications

(3 citation statements)

References 151 publications

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“…From the discovery of immunotherapy, with a single drug or in combination, a new era against cancer started. As explained for hematological malignancies, also in solid tumors immune checkpoint inhibitors, directed, for example, against programmed death protein-1 or the cytotoxic T lymphocyte antigen 4, are suitable permitting the reaching, in some cases, of superior results in terms of overall survival [49][50][51][52][53][54][55][56][57][58][59]. Oxidative stress, as is well known, has a pivotal role in cancerogenesis, in particular, the nuclear factor erythroid 2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) pathway is involved in chemoresistance in lung cancer through a stimulus to proliferation; in fact, an overexpression of HO-1 is related to higher tumor aggressivity [60].…”

Section: Lung Cancermentioning

confidence: 99%

Gender Differences and miRNAs Expression in Cancer: Implications on Prognosis and Susceptibility

Caserta

Gangemi

Murdaca

et al. 2023

IJMS

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MicroRNAs are small, noncoding molecules of about twenty-two nucleotides with crucial roles in both healthy and pathological cells. Their expression depends not only on genetic factors, but also on epigenetic mechanisms like genomic imprinting and inactivation of X chromosome in females that influence in a sex-dependent manner onset, progression, and response to therapy of different diseases like cancer. There is evidence of a correlation between miRNAs, sex, and cancer both in solid tumors and in hematological malignancies; as an example, in lymphomas, with a prevalence rate higher in men than women, miR-142 is “silenced” because of its hypermethylation by DNA methyltransferase-1 and it is blocked in its normal activity of regulating the migration of the cell. This condition corresponds in clinical practice with a more aggressive tumor. In addition, cancer treatment can have advantages from the evaluation of miRNAs expression; in fact, therapy with estrogens in hepatocellular carcinoma determines an upregulation of the oncosuppressors miR-26a, miR-92, and miR-122 and, consequently, apoptosis. The aim of this review is to present an exhaustive collection of scientific data about the possible role of sex differences on the expression of miRNAs and the mechanisms through which miRNAs influence cancerogenesis, autophagy, and apoptosis of cells from diverse types of tumors.

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Section: Lung Cancermentioning

confidence: 99%

Gender Differences and miRNAs Expression in Cancer: Implications on Prognosis and Susceptibility

Caserta

Gangemi

Murdaca

et al. 2023

IJMS

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“…In recent years, emerging blood-based biomarkers based on liquid biopsies have attracted much attention in the investigation of biomarkers for predicting immune efficacy in NSCLC, including circulating free tumor DNA (ctDNA), circulating non-coding RNAs (microRNAs), and peripheral blood immune cell populations. The evolution of epigenetic biomarkers and the gut microbiota are also receiving attention 27 .…”

Section: Othersmentioning

confidence: 99%

First-line immunotherapy for advanced non-small cell lung cancer: current progress and future prospects

Wang,

2023

Cancer Biol Med

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Global Cancer Statistics 2022 reported the prevalence and high mortality rate of lung cancer. Notably, non-small cell lung cancer (NSCLC) accounts for the majority of the histologic types 1 . Precision therapy for lung cancer has progressed rapidly and immune checkpoint inhibitors (ICIs) have become a leading research topic. Indeed, ICI therapy has been shown to improve the prognosis of lung cancer patients. ICI monotherapy or combination therapy has now become the first-line standard treatment option for patients with driver gene-negative advanced NSCLC 2 . Despite the clear progress being made in immunotherapy, many issues still need to be further explored, such as the selection of optimization strategies and the identification of efficacy-related biomarkers. Herein we will summarize the current status of first-line immunotherapy for NSCLC, discuss the research progress with respect to immunotherapy biomarkers, and clarify the challenges and future directions of first-line immunotherapy for NSCLC. Mechanism of action underlying ICIsThe ICIs that have been studied intensively include programmed cell death 1 (PD-1), programmed cell death ligand 1 (PD-L1), and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) inhibitors. PD-L1 is a co-regulatory molecule expressed on tumor cells and inhibits T cell-mediated cell death. T-cells express PD-1 (a negative regulator), which binds to ligands, including PD-L1 (CD274) and PD-L2 (CD273). PD-1/PD-L1 is a negatively regulated signaling pathway for T-cell activation. By blocking this pathway PD-1/PD-L1 inhibitors reactivate suppressed T-cells, enhance recognition of tumor antigens and kill tumor cells. CTLA-4 is another co-stimulatory molecule that negatively regulates T-cell activation. CTLA-4 inhibitors effectively block the binding of CTLA-4 to B7 molecules and restore the activity of the co-stimulatory CD28-B7 signaling pathway. Thus, the inhibitory effect on T cell activation is weakened and the infiltration of tumor-specific T cells is increased 2,3 . Current status of first-line immunotherapy for advanced NSCLCImmunotherapy has changed the landscape of first-line treatment for patients with advanced NSCLC. We have summarized immunotherapy regimens approved by the U.S. Food & Drug Administration (FDA) and/or the Chinese National Medical Products Administration (NMPA) for first-line treatment of advanced NSCLC. ICI monotherapyCurrently, pembrolizumab, atezolizumab, or cemiplimab monotherapy is recommended as first-line treatment for advanced NSCLC with high PD-L1 expression and negative driver genes regardless of histologic type (squamous or non-squamous; Table 1) 2 .Evidence for monotherapy with the PD-1 inhibitor, pembrolizumab, comes primarily from the KEYNOTE-024 and KEYNOTE-042 studies. The KEYNOTE-024 study included

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“…Patients who respond to immunotherapy have profound, durable improvements which lead to reduced mortality in patients [ 3 ]. However, less than 30% of patients respond to immunotherapies, and the identification of predictive biomarkers of patient response remains a challenge [ 4 ]. Targeted therapies often have limited efficacy and multiple adverse effects, and the predicament of drug resistance has severely restricted the long-term survival advantage for novel agents including KRAS G12C inhibitors [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

The Triterpenoid CDDO-Methyl Ester Reduces Tumor Burden, Reprograms the Immune Microenvironment, and Protects from Chemotherapy-Induced Toxicity in a Preclinical Mouse Model of Established Lung Cancer

Moerland,

Liby

2024

Antioxidants

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NRF2 activation protects epithelial cells from malignancy, but cancer cells can upregulate the pathway to promote survival. NRF2 activators including CDDO-Methyl ester (CDDO-Me) inhibit cancer in preclinical models, suggesting NRF2 activation in other cell types may promote anti-tumor activity. However, the immunomodulatory effects of NRF2 activation remain poorly understood in the context of cancer. To test CDDO-Me in a murine model of established lung cancer, tumor-bearing wildtype (WT) and Nrf2 knockout (KO) mice were treated with 50–100 mg CDDO-Me/kg diet, alone or combined with carboplatin/paclitaxel (C/P) for 8–12 weeks. CDDO-Me decreased tumor burden in an Nrf2-dependent manner. The combination of CDDO-Me plus C/P was significantly (p < 0.05) more effective than either drug alone, reducing tumor burden by 84% in WT mice. CDDO-Me reduced the histopathological grade of WT tumors, with a significantly (p < 0.05) higher proportion of low-grade tumors and a lower proportion of high-grade tumors. These changes were augmented by combination with C/P. CDDO-Me also protected WT mice from C/P-induced toxicity and improved macrophage and T cell phenotypes in WT mice, reducing the expression of CD206 and PD-L1 on macrophages, decreasing immunosuppressive FoxP3+ CD4+ T cells, and increasing activation of CD8+ T cells in a Nrf2-dependent manner.

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Potential biomarkers for immunotherapy in non-small-cell lung cancer

Cited by 6 publications

References 151 publications

Gender Differences and miRNAs Expression in Cancer: Implications on Prognosis and Susceptibility

Gender Differences and miRNAs Expression in Cancer: Implications on Prognosis and Susceptibility

First-line immunotherapy for advanced non-small cell lung cancer: current progress and future prospects

The Triterpenoid CDDO-Methyl Ester Reduces Tumor Burden, Reprograms the Immune Microenvironment, and Protects from Chemotherapy-Induced Toxicity in a Preclinical Mouse Model of Established Lung Cancer

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