Meeting Immunotherapy Resistance in Lung Cancer

Leighl, Natasha B.

doi:10.1016/j.jtho.2020.11.018

Cited by 6 publications

(5 citation statements)

References 22 publications

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“…no benefit in others (48)(49)(50). Therefore, it is important to authenticate new LUAD subtypes for providing precise treatment and prognosis prediction for patients.…”

Section: Discussionmentioning

confidence: 99%

Molecular typing and prognostic model of lung adenocarcinoma based on cuprotosis-related lncRNAs

Zheng¹,

Zhou²,

Xie³

et al. 2022

J Thorac Dis

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Background: Previous research has shown the heterogeneity of lung adenocarcinoma (LUAD) accounts for the different effects and prognoses of the same treatment. Cuprotosis is a newly discovered form of programmed cell death involved in the development of tumors. Therefore, it is important to study the long non-coding RNAs (lncRNAs) that regulate cuprotosis to identify molecular subtypes and predict survival of LUAD. Methods: The expression profile, clinical, and mutation data of LUAD were downloaded from The Cancer Genome Atlas (TCGA), and the "ConsensusClusterPlus" package was used to cluster LUADs based on cuprotosis-related lncRNAs (CR-lncRNAs). The least absolute shrinkage and selection operator (Lasso) and multivariate Cox regression were used to construct a prognostic model. CIBERSORT and singlesample gene set enrichment analysis (ssGSEA) were used for assessing immune cells infiltration and immune function. The tumor microenvironment (TME) score was calculated by ESTIMATE, and the tumor mutational burden (TMB) and Tumor Immune Dysfunction and Exclusion (TIDE) were used to evaluate the efficacy of immunotherapy.Results: Firstly, 501 CR-lncRNAs were identified based on the co-expression relationship of 19 cuprotosis genes. And univariate Cox further obtained 34 prognosis-related CR-lncRNAs. The unsupervised consensus clustering divided LUAD samples into cluster A and cluster B, and showed cluster A had better prognosis, more immune cells infiltration, stronger immune function, and a higher TME score. Subsequently, we used Lasso Cox regression to construct a prognostic model, and univariate and multivariate Cox analyses showed the risk score could be an independent prognostic indicator. Immune cells infiltration, immune function, and TME score were increased markedly in the low-risk group, while TMB and TIDE suggested the efficacy of immunotherapy might be increased in high-risk group.Conclusions: Our research identified two new molecular subtypes and constructed a novel prognostic model of LUAD which could provide new direction for its diagnosis, treatment, and prognosis.

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“…no benefit in others (48)(49)(50). Therefore, it is important to authenticate new LUAD subtypes for providing precise treatment and prognosis prediction for patients.…”

Section: Discussionmentioning

confidence: 99%

Molecular typing and prognostic model of lung adenocarcinoma based on cuprotosis-related lncRNAs

Zheng¹,

Zhou²,

Xie³

et al. 2022

J Thorac Dis

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“…Accurate biomarkers to predict ICI response among lung cancer patients is currently lacking. Beyond PD-L1 tumour proportion score (TPS), other biomarkers such as tumour mutation burden (TMB), specific tumour mutations in TP53 and KRAS genes, inflammatory signatures including gamma interferon signalling and tumour-infiltrating lymphocytes (TIL) density have also been explored to predict benefit from anti-PD-1 agents [ 7 , 8 ]. Interestingly, several studies and clinical experience have shown that patients that are current or former smokers appear to have improved outcomes with anti-PD-1 therapy compared to never smokers [ 9 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

Tobacco Use and Response to Immune Checkpoint Inhibitor Therapy in Non-Small Cell Lung Cancer

Corke

Leighl

et al. 2022

Current Oncology

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Tobacco is a known risk factor for lung cancer, and continued tobacco use is associated with poorer outcomes across multiple lung cancer treatment modalities including surgery, chemotherapy and radiation therapy. Less is known about the association of tobacco use and outcomes with immune checkpoint inhibitors (ICIs), which are becoming an important part of the treatment landscape in lung cancer, both in metastatic and curative settings. We reviewed the literature on the association of tobacco and tumor biology as it relates to immunotherapy. We also reviewed the association of tobacco use on outcomes among phase III randomized clinical trials involving ICIs in non-small cell lung cancer (NSCLC). We identified that patients with a smoking history may have a greater benefit with ICI treatment compared to never smokers in both treatment-naïve (HR 0.82, 95% CI 0.69–0.97, vs. HR 1.06, 95% CI 0.81–1.38) and pre-treated (HR 0.79, 95% CI 0.70–0.90 vs. 1.03, 95% CI 0.74–1.43) settings. In trials where smoking status was further defined, ex-smokers appear to demonstrate greater benefit with ICI therapy compared to current smokers (HR 0.78, 95% CI 0.59–1.01 vs. 0.91, 95% CI 0.72–1.14). We conclude by offering our perspective on future directions in this area of research, including implementation of standardized collection and analysis of tobacco use in clinical trials involving ICI therapy in lung cancer and other disease sites, and also evaluating how tobacco may affect toxicities related to ICI therapy. Based on our review, we believe that a patient’s history of tobacco smoking does have a role to play in guiding treatment decision making in patients with lung cancer.

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“…In canceration, PD-L1 can disrupt the tumor's immune cycle in two ways, thus protecting the tumor from damage by cytotoxic T cells. First, over-expression of PD-L1 on the surface of tumorinfiltrating immune cells in lymph nodes prevents the initiation and activation of new cytotoxic T cells and their recruitment into the tumor (52). Secondly, in the tumor microenvironment, the up-regulation of PD-L1 on the surface of dendritic cells leads to the inactivation of cytotoxic t cells.…”

Section: Pd-1/pd-l1 and Tumor Immunotherapymentioning

confidence: 99%

The Mechanism of Stimulating and Mobilizing the Immune System Enhancing the Anti-Tumor Immunity

Zhu

2021

Front. Immunol.

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Cancer immunotherapy is a kind of therapy that can control and eliminate tumors by restarting and maintaining the tumor-immune cycle and restoring the body’s normal anti-tumor immune response. Although immunotherapy has great potential, it is currently only applicable to patients with certain types of tumors, such as melanoma, lung cancer, and cancer with high mutation load and microsatellite instability, and even in these types of tumors, immunotherapy is not effective for all patients. In order to enhance the effectiveness of tumor immunotherapy, this article reviews the research progress of tumor microenvironment immunotherapy, and studies the mechanism of stimulating and mobilizing immune system to enhance anti-tumor immunity. In this review, we focused on immunotherapy against tumor microenvironment (TME) and discussed the important research progress. TME is the environment for the survival and development of tumor cells, which is composed of cell components and non-cell components; immunotherapy for TME by stimulating or mobilizing the immune system of the body, enhancing the anti-tumor immunity. The checkpoint inhibitors can effectively block the inhibitory immunoregulation, indirectly strengthen the anti-tumor immune response and improve the effect of immunotherapy. We also found the checkpoint inhibitors have brought great changes to the treatment model of advanced tumors, but the clinical treatment results show great individual differences. Based on the close attention to the future development trend of immunotherapy, this study summarized the latest progress of immunotherapy and pointed out a new direction. To study the mechanism of stimulating and mobilizing the immune system to enhance anti-tumor immunity can provide new opportunities for cancer treatment, expand the clinical application scope and effective population of cancer immunotherapy, and improve the survival rate of cancer patients.

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Meeting Immunotherapy Resistance in Lung Cancer

Cited by 6 publications

References 22 publications

Molecular typing and prognostic model of lung adenocarcinoma based on cuprotosis-related lncRNAs

Molecular typing and prognostic model of lung adenocarcinoma based on cuprotosis-related lncRNAs

Tobacco Use and Response to Immune Checkpoint Inhibitor Therapy in Non-Small Cell Lung Cancer

The Mechanism of Stimulating and Mobilizing the Immune System Enhancing the Anti-Tumor Immunity

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