scholarly journals A comprehensive profiling of soluble immune checkpoints from the sera of patients with non‐small cell lung cancer

Author(s):  
Ying Peng ◽  
Chen Zhang ◽  
Zhilian Rui ◽  
Weiming Tang ◽  
Yan Xu ◽  
...  
2021 ◽  
Vol 6 (5) ◽  
Author(s):  
Wang J ◽  
Deng C ◽  
Zhu X ◽  
Zou X ◽  
Wang J

In recent years, extraordinary achievements have been made in treating tumor immune checkpoints as targets, which significantly contributes to the research and development of novel immunologic drugs and their application in treating malignant tumors. However, few immunologic drugs can be administered to treat Small Cell Lung Cancer (SCLC). Currently, the focus of most clinical studies is placed on treating SCLC with a combination of immunotherapy and chemotherapy, which is relatively expensive and not covered by medical insurance, thus imposing a heavy economic burden on patients. Meanwhile, obvious adverse reactions occur during chemotherapy, which is still unacceptable to many patients and hence has not yet been widely adopted in clinical practice. Therefore, whether immunotherapy alone can help patients with SCLC, improve their quality of life, and prolong their survival time is a topic we will study in the future. In this case, an attempt was made to apply camrelizumab, an immunologic drug, in the treatment of SCLC in advanced stages, and a favorable efficacy was achieved.


ESMO Open ◽  
2018 ◽  
Vol 3 (5) ◽  
pp. e000349 ◽  
Author(s):  
Ana Luísa Coelho ◽  
Mónica Patrícia Gomes ◽  
Raquel Jorge Catarino ◽  
Christian Rolfo ◽  
Rui Manuel Medeiros ◽  
...  

BackgroundLung cancer is the most incident and lethal form of cancer, with late diagnosis as a major determinant of its bad prognosis. Immunotherapies targeting immune checkpoints improve survival, but positive results encompass only 30%–40% of the patients, possibly due to alternative pathways to immunosuppression, including tumour-associated macrophages (TAM). Colony stimulating factor-1 (CSF-1) is implicated in TAM differentiation and recruitment to tumours and in tumour angiogenesis, through a special setting of Tie-2-expressing macrophages, which respond to angiopoietin-2 (Ang-2). We evaluated the role of serum levels of CSF-1 in non-small cell lung cancer (NSCLC) prognosis and whether these could serve as biomarkers for NSCLC detection, along with Ang-2.Participants and methodsWe prospectively studied an unselected cohort of 145 patients with NSCLC and a group of 30 control individuals. Serum levels of Ang-2 and CSF-1 were measured by ELISA prior to treatment.ResultsSerum levels of CSF-1 and Ang-2 are positively correlated (p<0.000001). Individuals with high serum levels of CSF-1 have a 17-fold risk for NSCLC presence and patients with combined High Ang-2/CSF-1 serum levels present a 5-fold increased risk of having NSCLC. High Ang-2/CSF-1 phenotype is also associated with worst prognosis in NSCLC.ConclusionsCombined expression of CSF-1 and Ang-2 seems to contribute to worst prognosis in NSCLC and it is worthy to understand the basis of this unexplored partnership. Moreover, we think CSF-1 could be included as a biomarker in NSCLC screening protocols that can improve the positive predictive value of the current screening modalities, increase overall cost effectiveness and potentially improve lung cancer survival.


2015 ◽  
Vol 11 (01) ◽  
pp. 36
Author(s):  
Adrian G Sacher ◽  
Leena Gandhi ◽  
◽  

There exists increasing evidence that PD-1 and PD-L1 inhibitors may be effective in the treatment of non-small cell lung cancer (NSCLC)— an unforeseen finding given the early failure of several immuno- and vaccine-based therapies in this field. This suggests that NSCLC is a more immunogenic tumor than initially appreciated and that it may manipulate various immune checkpoints in order to blunt a potential anti-tumor immune response. NSCLC has subsequently been shown to commonly overexpress PD-L1 as a means of suppressing such cell-mediated immune response through PD-1-mediated signaling. Numerous PD-1 and PD-L1 inhibitors are currently in development as well as various combinations of these inhibitors with chemotherapy, kinase inhibitors, and other immune checkpoint inhibitors. Although these treatments have demonstrated clinical activity in early phase clinical trials, reliable data on the impact of these agents on clinically meaningful endpoints in advanced NSCLC remains scarce. Important questions remain unanswered regarding the appropriate use of PD-L1 expression as a predictive biomarker for the use of these agents as well as the ability of the aforementioned drug combinations to achieve durable disease control.


2021 ◽  
Vol 22 (5) ◽  
Author(s):  
Lin-Rui Ma ◽  
Jia-Xin Li ◽  
Ling Tang ◽  
Run-Ze Li ◽  
Jia-Shun Yang ◽  
...  

2020 ◽  
Author(s):  
David Dora ◽  
Christopher Rivard ◽  
Hui Yu ◽  
Paul Bunn ◽  
Kenichi Suda ◽  
...  

ABSTRACTSmall cell lung cancer (SCLC) has recently been sub-categorized into neuroendocrine (NE)- high and NE-low subtypes showing ‘immune desert’ and ‘immune oasis’ phenotypes, respectively. We aimed to characterize the immune cell localization and the microenvironment according to immune checkpoints and NE subtypes in human SCLC tissue samples at the protein level. In this cross-sectional study, we included 32 primary tumors and matched lymph node (LN) metastases of resected early-stage, histologically confirmed SCLC patients, which were previously clustered into NE subtypes using NE-associated key RNA genes. Immunohistochemistry (IHC) was performed on FFPE TMAs with antibodies against CD45, CD3, CD8 and immune checkpoints including poliovirus receptor (PVR) and Indoleamine 2,3-dioxygenase (IDO).According to our results, the stroma was significantly more infiltrated by immune cells both in primary tumors and LN metastases (vs tumor cell nests). Immune (CD45+) cell density was significantly higher in tumor nests (110.6 ± 24.95 vs 42.74 ± 10.30, cell/mm2, p= 0.0048), with increased CD8+ effector T cell infiltration (21.81 ± 5.458 vs 3.16 ± 1.36 cell/mm2, p < 0.001) in NE-low vs NE-high tumors. Furthermore, the expression of IDO was confirmed on stromal and endothelial cells, and it positively correlated (r= 0.755, p<0.01) with higher immune cell density both in primary tumors and LN metastases, regardless of the NE pattern. Expression of IDO in tumor nests was significantly higher in NE-low (vs NE-high) primary tumors. PVR expression was significantly higher in NE-low (vs NE-high) patients both in primary tumors) and LN metastases.To our knowledge, this is the first human study that demonstrates in situ that NE-low tumors are associated with increased immune cell infiltration compared to NE-high tumors. PVR and IDO are potential new targets in SCLC, with increased expression in the NE-low subtype, providing key insight for further prospective studies on potential biomarkers and targets for SCLC immunotherapies.


2016 ◽  
Vol 12 (01) ◽  
pp. 15
Author(s):  
Maurice Pérol ◽  

In parallel with the evolution of therapeutic paradigms for advanced cancers, treatment of advanced non-small cell lung cancer (NSCLC) has been through the revolution of personalised medicine benefiting for a minority of patients whose disease depends on a single oncogenic genetic alteration targetable by specific tyrosine kinase inhibitors. As well as for some other tumour types, targeting immune checkpoints inhibitors has shown encouraging activity for some patients, suggesting the dawn of a second therapeutic revolution for a significant proportion of lung cancer patients.


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