Immune checkpoint blockade and biomarkers of clinical response in non–small cell lung cancer

Hallqvist, Andreas; Rohlin, Anna; Raghavan, Sukanya

doi:10.1111/sji.12980

Cited by 18 publications

(16 citation statements)

References 77 publications

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“…Currently, several promising biomarkers for ICI therapy have been widely investigated, such as tumor mutation burden (TMB), PD-L1 expression, germline genotype of HLA-I, the molecular profiling of the tumor microenvironment, mutations in DNA mismatch repair and replication genes ( 1 , 5 , 6 ). However, most of these biomarkers are far from perfect biomarkers owing to being invasive, not always feasible, and its spatial and temporal heterogeneity ( 6 , 7 ).…”

Section: Introductionmentioning

confidence: 99%

The Role of Circulating Tumor DNA in Advanced Non-Small Cell Lung Cancer Patients Treated With Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis

et al. 2021

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BackgroundThe use of circulating tumor DNA (ctDNA) to reflect clinical benefits of advanced non-small cell lung cancer (NSCLC) patients during immune checkpoint inhibitor (ICI) therapy remains controversial. This study aimed to determine the association of pre-treatment and early dynamic changes of ctDNA with clinical outcomes in advanced NSCLC patients treated with ICIs.MethodsElectronic databases (PubMed, Embase, Web of Science, and Cochrane) were systematically searched to include relevant studies published in English up to November 2020. The primary outcomes were overall survival (OS) and progression-free survival (PFS) and the secondary outcome was objective response rate (ORR) with RECIST criteria.ResultsA total of 1017 patients from 10 studies were identified. The baseline ctDNA levels (detected versus not detected) showed no significant association with clinical outcomes regarding OS (hazard ratio [HR], 1.18; 95% confidence interval [CI], 0.93-1.51), PFS (HR, 0.98; 95% CI, 0.80-1.21), and ORR (odds ratio [OR], 0.89; 95% CI, 0.54-1.46). Interestingly, when taken early longitudinal assessment of ctDNA into consideration, the early reduction of the concentration of ctDNA was associated with significant improvements of OS (HR, 0.19; 95% CI, 0.10-0.35), PFS (HR, 0.30; 95% CI, 0.22-0.41) and ORR (OR, 0.07; 95% CI, 0.03-0.18). Further subgroup analyses revealed that the reduction magnitude did not significantly impact the association between ctDNA and clinical outcomes, suggesting that both patients with decreased ctDNA or a ≥50% reduction of ctDNA was associated with improved OS, PFS and ORR.ConclusionEarly reduction of ctDNA was associated with improved OS, PFS and ORR in advanced NSCLC patients treated with ICIs.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO, CRD42021226255.

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Section: Introductionmentioning

confidence: 99%

The Role of Circulating Tumor DNA in Advanced Non-Small Cell Lung Cancer Patients Treated With Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis

et al. 2021

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“…There is no effective treatment for this debilitating disease so far. Anti-PD-1 and anti-CTLA-4 antibodies have been recently developed as checkpoint reagents in the treatment of various cancer patients including Hodgkin lymphoma and showing some promising results in clinical trials [2][3][4]. Other reagents, such as TIM-3, TIGIT, BTLA, CD47, and KIR that target the adaptive and innate immune system are recently developed as alternative ways to activate the immune system [5].…”

Section: Introductionmentioning

confidence: 99%

CD4-Targeted T Cells Rapidly Induce Remissions in Mice with T Cell Lymphoma

Cheng

Chen

et al. 2021

BioMed Research International

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Objective. To explore the immune cell therapy for T cell lymphoma, we developed CD4-specific chimeric antigen receptor- (CAR-) engineered T cells (CD4CART), and the cytotoxic effects of CD4CART cells were determined in vitro and in vivo. Methods. CD4CART cells were obtained by transduction of lentiviral vector encoding a single-chain antibody fragment (scFv) specific for CD4 antigen, costimulatory factor CD28 fragment, and intracellular signal transduction domain of CD3 fragments. Control T cells were obtained by transduction of reporter lentiviral vector. The cytotoxicity, tumor growth, and survival rate of mice with T cell lymphoma were analyzed after adoptive T cell transfer in vivo. Results. CD4CART cells had potent cytotoxic activity against CD4+ T1301 tumor T cells in a concentration-dependent manner. In addition, adoptive CD4CART cell transfer significantly suppressed tumor growth and improved animal survival with T cell lymphoma, compared to the mice who received control T cells and PBS. Conclusion. CD4CART cells have potent cytotoxic effects on T cell lymphoma. The study provided an experimental basis for CD4CART-mediated therapy of T cell lymphoma.

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“…Substantial progress in cancer treatment is the development of immune checkpoint inhibitors (ICI) such as an anti-cytotoxic Tlymphocyte antigen 4 (CTLA4) monoclonal antibodies (mAb) (ipilimumab) and anti-programmed death-1 (PD-1) mAbs (nivolumab and pembrolizumab), able to overcome the tumorinduced immune escape [182][183][184]. This pharmacological approach has led to long-term survival in patients with several kinds of cancer, including melanoma, cervical, breast, and nonsmall-cell lung cancer [186][187][188], and its use is increasing in clinical practice. Unfortunately, the ICI efficacy is observed in a small proportion of treated patients, and drug resistance development often occurs.…”

Section: Platelet Engineeringmentioning

confidence: 99%

Multifaceted Functions of Platelets in Cancer: From Tumorigenesis to Liquid Biopsy Tool and Drug Delivery System

Dovizio¹,

Ballerini²,

Fullone³

et al. 2021

Prime Archives in Molecular Sciences

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Platelets contribute to several types of cancer through plenty of mechanisms. Upon activation, platelets release many molecules, including growth and angiogenic factors, lipids, and extracellular vesicles, and activate numerous cell-types, including vascular and immune cells, fibroblasts, and cancer cells. Hence, platelets are a crucial component of cell-cell communication. In particular, their interaction with cancer cells can enhance their malignancy and facilitate the invasion and colonization of distant organs. These findings suggest the use of antiplatelet agents to restrain cancer development and progression. Another peculiarity of platelets is their capability to uptake proteins and transcripts from the circulation. Thus, cancer patient platelets show specific proteomic and transcriptomic expression patterns, a phenomenon called tumor-educated platelets (TEP). The Prime Archives in Molecular Sciences: 2 nd Edition 3 www.videleaf.com transcriptomic/proteomic profile of platelets can provide information for the early detection of cancer and disease monitoring. Platelet ability to interact with tumor cells and transfer their molecular cargo has been exploited to design platelet-mediated drug delivery systems to enhance the efficacy and reduce toxicity often associated with traditional chemotherapy. Platelets are extraordinary cells with many functions whose exploitation will improve cancer diagnosis and treatment.

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Immune checkpoint blockade and biomarkers of clinical response in non–small cell lung cancer

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 18 publications

References 77 publications

The Role of Circulating Tumor DNA in Advanced Non-Small Cell Lung Cancer Patients Treated With Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis

The Role of Circulating Tumor DNA in Advanced Non-Small Cell Lung Cancer Patients Treated With Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis

CD4-Targeted T Cells Rapidly Induce Remissions in Mice with T Cell Lymphoma

Multifaceted Functions of Platelets in Cancer: From Tumorigenesis to Liquid Biopsy Tool and Drug Delivery System

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