Role of Immune Checkpoint Inhibitors in Small Cell Lung Cancer

Cooper, Michael; Alrajhi, Abdullah M; Durand, Cheryl

doi:10.1097/mjt.0000000000000686

Cited by 12 publications

(10 citation statements)

References 23 publications

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“…Determining the underlying mechanism of the suppressive antitumor immunity might help to develop precise immunotherapy strategies for this deadly cancer. Immunotherapy, especially immune checkpoint inhibitors, has achieved great success in many solid tumors, including SCLC 27 and ESCC, 28 both of which share similarities to SCCE. 12 Thus, we explored the potential efficacy of immunotherapy on SCCE.…”

Section: Discussionmentioning

confidence: 99%

Systematic analysis of the transcriptome in small‐cell carcinoma of the oesophagus reveals its immune microenvironment

Zhao

Chen

et al. 2020

Clin & Trans Imm

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Objectives. Although the genomic landscape of small-cell carcinoma of the oesophagus (SCCE) has been dissected, its transcriptome-level aberration and immune microenvironment status are unknown. Methods. Using ultra-deep whole transcriptome sequencing, we analysed the expression profile of nine paired SCCE samples and compared the transcriptome with public transcriptomic data set of normal oesophageal mucosa and other cancer types. Based on the transcriptome data, the immune signatures were investigated. The genomic data of 55 SCCE samples were also applied for immune checkpoint blockade therapy (ICBT) biomarker evaluation including microsatellite instability (MSI) status, tumor mutation burden (TMB) and neoantigen burden (TNB). Also, we evaluated the CD8, CD68 and programmed death-ligand 1 (PD-L1) in 62 retrospective SCCE samples with IHC assay. Results. Differential expression analysis revealed that the cell cycle, p53, and Wnt pathways are significantly deregulated in SCCE. Immune microenvironment analysis showed that high leucocyte infiltration and adaptive immune resistance did occur in certain individuals, while the majority showed a relatively suppressive immune status. Immune checkpoints such as CD276 and LAG-3 were upregulated, and higher M2 macrophage infiltration in tumor tissues. Furthermore, normal tissues adjacent to the tumors of SCCE presented a more activated inflammatory status than tumorfree healthy controls. These observations showed that ICBT might benefit SCCE patients. As the critical biomarker of ICBT, TMB of SCCE was 3.64 with the predictive objective response rate 13.2%, while the PD-L1-positive rate was 43%. Conclusions. Our study systematically characterized the immune microenvironment in small-cell carcinoma of the esophagus and provided evidence that several patients with SCCE may benefit from immune checkpoint blockade therapy.

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Section: Discussionmentioning

confidence: 99%

Systematic analysis of the transcriptome in small‐cell carcinoma of the oesophagus reveals its immune microenvironment

Zhao

Chen

et al. 2020

Clin & Trans Imm

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“…48 The NCCN panel recently added recommendations for nivolumab and nivolumab + ipilimumab (both are category 2A) as subsequent therapy options for patients who have experienced disease relapse ≤6 months after primary therapy. 49 These recommendations are based on a phase I/II trial of patients who received either nivolumab alone or various doses of nivolumab + ipilimumab for relapsed SCLC. 50 Response rates were 10% (10/98) for nivolumab at 3 mg/kg; 23% (14/61) for nivolumab at 1 mg/kg + ipilimumab at 3 mg/kg; and 19% (10/54) for nivolumab at 3 mg/kg + ipilimumab at 1 mg/kg.…”

Section: Second-line and Beyond (Subsequent) Systemic Therapymentioning

confidence: 99%

NCCN Guidelines Insights: Small Cell Lung Cancer, Version 2.2018

Kalemkerian¹,

Loo

Akerley

et al. 2018

J Natl Compr Canc Netw

219

179

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The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines ®) are a statement of consensus of the authors regarding their views of currently accepted approaches to treatment. The NCCN Guidelines ® Insights highlight important changes in the NCCN Guidelines ® recommendations from previous versions. Colored markings in the algorithm show changes and the discussion aims to further understanding of these changes by summarizing salient portions of the panel's discussion, including the literature reviewed. The NCCN Guidelines Insights do not represent the full NCCN Guidelines; further, the National Comprehensive Cancer Network® (NCCN ®) makes no representation or warranties of any kind regarding the content, use, or application of the NCCN Guidelines and NCCN Guidelines Insights and disclaims any responsibility for their applications or use in any way. The full and most current version of these NCCN Guidelines is available at NCCN.org.

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“…These data have important implications for the use of CTCs as a liquid biopsy (13,27,28). Using a microfluidic device, the expected activating EGFR mutations identified in the original tumor biopsy specimens have also been detected in CTCs from 11 of 12 patients with lung cancer (92%) (4). More recently, a novel in vivo device was used to capture circulating lung cancer cells from one patient, and the same EGFR mutations identified in the primary tumors were clearly detectable in the collected CTCs (29).…”

Section: Discussionmentioning

confidence: 99%

“…These alterations are attributed to a decrease in tobacco use, the progress in lung cancer screening with low-dose computed tomography, and improvements in treatment in recent years (1). Novel targeted treatments for advanced non-small-cell lung cancer (NSCLC) based on driver mutations and immune checkpoints are continuously being developed (2–4). Epidermal growth factor receptor (EGFR) mutations are the most frequent driver mutations detected in lung adenocarcinomas and exhibit clinically therapeutic implications.…”

Section: Introductionmentioning

confidence: 99%

Isolation of circulating tumor cells and detection of EGFR mutations in patients with non‑small‑cell lung cancer

et al. 2019

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The aim of the present study was to develop a procedure for the isolation of circulating tumor cells (CTCs), and to evaluate its application in the detection of epidermal growth factor receptor (EGFR) mutations, and potential heterogeneity in patients with non-small-cell lung cancer (NSCLC). Peripheral blood samples were collected from 91 patients with lung cancer, 10 patients with benign disease and 10 healthy volunteers. CTCs were enriched by positive immunomagnetic separation, detected by immunocytochemistry, and processed for single-cell capture. Pure CTC DNA was amplified, and the EGFR gene was analyzed using the amplification refractory mutation system (ARMS) and digital polymerase chain reaction (dPCR). The CTC capture rate in patients with lung cancer was 61.5% (56/91), whereas no CTCs were detected in patients with benign lung disease or in healthy volunteers. The CTC-positive detection rates were 69.3% (52/75) and 25.0% (4/16) in patients with TNM stage III and IV disease, respectively. Markedly more CTCs were captured from patients with small-cell lung cancer compared with patients with other types of cancer. In patients who were positive for EGFR mutations, the detection rate of these mutations was low (16.67%, 2/12), at the single CTC level. The sensitivity increased as the number of CTCs per sample increased. A total of four patients displayed consistent detection of EGFR mutations at the 10-cell level, and one patient exhibited a clear, inconsistent and rare mutation (G719x) between CTCs. A simplified technique for isolating CTCs from blood was established, though multiple CTCs were required to sensitively detect mutations in these cells. The detection of EGFR mutations in CTCs and tissue specimens was generally homogeneous, and therefore, the CTC-level mutation analysis may potentially contribute to the discovery of heterogeneous mutations.

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Role of Immune Checkpoint Inhibitors in Small Cell Lung Cancer

Abstract: Given the lack of overall survival data and significant toxicity associated with the combination of ipilimumab with first-line chemotherapy, this treatment is not a reasonable option at this time. Nivolumab alone or in combination with ipilimumab is a valid option for recurrent SCLC.

Cited by 12 publications

References 23 publications

Systematic analysis of the transcriptome in small‐cell carcinoma of the oesophagus reveals its immune microenvironment

Systematic analysis of the transcriptome in small‐cell carcinoma of the oesophagus reveals its immune microenvironment

NCCN Guidelines Insights: Small Cell Lung Cancer, Version 2.2018

Isolation of circulating tumor cells and detection of EGFR mutations in patients with non‑small‑cell lung cancer

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