The potentiality of immunotherapy for sarcomas: a summary of potential predictive biomarkers

2020 ◽  
Vol 16 (17) ◽  
pp. 1211-1223 ◽  
Author(s):  
Jin Liang ◽  
Dedian Chen ◽  
Liyao Chen ◽  
Xueke She ◽  
Hushan Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Side Effects ◽  
Malignant Tumors ◽  
Immune Surveillance ◽  
Predictive Biomarkers ◽  
Small Cell ◽  
Small Cell Lung ◽  
Curative Intent ◽  
Metastatic Setting ◽  
Potential Biomarkers

Sarcomas are rare and heterogeneous malignant tumors of mesenchymal origin. A total of 25–50% of patients treated with initial curative intent will develop as recurrent and metastatic disease. In the recurrent and metastatic setting, effect of chemotherapy is limited; therefore, more effective therapies are urgently desired. As a brake for activation of T cell, PD-1/PD-L1 plays a crucial role in the progression of tumor by altering status of immune surveillance. Some success has been acquired recently in the use of PD-1/PD-L1 inhibitors for the treatment of several solid tumors, for examples, non-small-cell lung cancer and melanoma. Immunotherapeutic strategies based on PD-1/PD-L1 for sarcomas have also been explored these years. As in other cancers, major challenges are identification of biomarkers to predict response for immunotherapy, optimization of patient’s benefit and minimization of side effects. Therefore, we focused on potential biomarkers of immunotherapy for treatment of sarcomas in this review.

Automated brightfield multiplex immunohistochemistry to quantify biomarkers related to immune senescence: Relationships with survival in non-small cell lung cancer patients.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e20500-e20500 ◽  
Author(s):  
Paul Hofman ◽  
Mélanie Beaulande ◽  
Saima Ben Hadj ◽  
Gilles Erb ◽  
Jean-François Pomerol ◽  
...  
Keyword(s):  
Lung Cancer ◽  
T Cells ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Immune Surveillance ◽  
Disease Free Survival ◽  
Predictive Biomarkers ◽  
Small Cell ◽  
Small Cell Lung ◽  
Nsclc Patients

e20500 Background: Elderly patients have an eroded immune characterized by a progressive decline in immune surveillance that favors infection and cancer development. Tumor cells can escape immune surveillance by upregulating inhibitory immune checkpoint such as PD-L1. High expression of PD-L1 was reported in association with CD8+T-cell exhaustion and increased levels of CD33+ myeloid-derived suppressor cells. Although low CD4/CD8 ratio is associated with increased mortality, the status of the CD4+T-cells as a clinical marker of immunosenescence is less well characterized in the field of aging. The aim of this study was to determine the presence of immunosenescence biomarkers according to age in non-small cell lung cancer (NSCLC) patients and to evaluate them as predictive biomarkers of patients’ outcome. Methods: One hundred NSCLC patients, matched by age (50 patients < 70 years, 50 patients ≥70 years) were included. An automated 4-Plex optical IHC assay was developed on the Discovery ULTRA automated stainer using monoclonal antibodies PD-L1 (SP263), CD4, CD8, and CD33. The stained slides were scanned with Nanozoomer HT 2.0 Scanner, and analyzed with Calopix software. Results: The CD4/CD8 ratio and PD-L1 expression in tumor and immune cells were significantly lower in elderly NSCLC patients ≥70 years than in age-paired patients, while absolute count of CD33+ was increased. Patients with CD4/CD8 ratio higher than two, high PD-L1 density and low CD33+ frequency achieved increase in median disease-free survival. Conclusions: Distribution of PD-L1, CD4, CD8, and CD33 cells was influenced by age in NSCLC patients. The proportion of CD8 + CD28- T cells, CD4+ T cells and CD4/CD8 ratio may be used as predictive biomarkers of anti-PD-L1 therapy efficacy in NSCLC patients. The automated 4-Plex IHC assay together with its respective digital analysis could serve as a tool for further characterizing tumors and their microenvironment and provide a better understanding of which patients may benefit from immunotherapy.

scholarly journals P09.22 Curative Intent Treatment for Small Cell Lung Cancer in England

2021 ◽  
Vol 16 (3) ◽  
pp. S298-S299
Author(s):  
S. Harden ◽  
E. Peach ◽  
P. Beckett ◽  
N. Navani
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Curative Intent

scholarly journals Chemo-immunotherapy as first-line treatment for small-cell lung cancer

2020 ◽  
Vol 12 ◽  
pp. 175883592098036
Author(s):  
Saira Farid ◽  
Stephen V. Liu
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Predictive Biomarkers ◽  
High Response Rate ◽  
Small Cell ◽  
Standards Of Care ◽  
Small Cell Lung ◽  
First Line ◽  
Line Chemotherapy

Small-cell lung cancer (SCLC) is a highly lethal subtype of lung cancer. Despite concerted efforts over the past several decades, there have been limited therapeutic advances. Traditional chemotherapy offers a high response rate and rapid symptomatic improvement, but its benefit is fleeting, and relapse is quick and unforgiving. Immunotherapy has delivered improved outcomes for patients with many cancers and there was compelling rationale for development in SCLC. While initial efforts with cytotoxic T-lymphocyte protein-4 inhibitors failed to improve upon chemotherapy alone, the addition of programmed death ligand-1 (PD-L1) inhibitors to first-line chemotherapy finally provided long-awaited gains in survival. Atezolizumab, when added to carboplatin and etoposide, improved both progression-free survival and overall survival. Durvalumab, when added to platinum plus etoposide, similarly improved OS. Biomarker development has stalled as PD-L1 expression and tumor mutational burden have not been useful predictive biomarkers. However, based on the significant survival improvements, both atezolizumab and durvalumab were approved by the US Food and Drug Administration to be given with first-line chemotherapy, and these regimens represent the new standards of care for SCLC.

scholarly journals Protein Kinase C as a Therapeutic Target in Non-Small Cell Lung Cancer

2021 ◽  
Vol 22 (11) ◽  
pp. 5527
Author(s):  
Mohammad Mojtaba Sadeghi ◽  
Mohamed F. Salama ◽  
Yusuf A. Hannun
Keyword(s):  
Lung Cancer ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Predictive Biomarkers ◽  
Small Cell ◽  
Small Cell Lung ◽  
Kinase C ◽  
Pkc Isozymes

Driver-directed therapeutics have revolutionized cancer treatment, presenting similar or better efficacy compared to traditional chemotherapy and substantially improving quality of life. Despite significant advances, targeted therapy is greatly limited by resistance acquisition, which emerges in nearly all patients receiving treatment. As a result, identifying the molecular modulators of resistance is of great interest. Recent work has implicated protein kinase C (PKC) isozymes as mediators of drug resistance in non-small cell lung cancer (NSCLC). Importantly, previous findings on PKC have implicated this family of enzymes in both tumor-promotive and tumor-suppressive biology in various tissues. Here, we review the biological role of PKC isozymes in NSCLC through extensive analysis of cell-line-based studies to better understand the rationale for PKC inhibition. PKC isoforms α, ε, η, ι, ζ upregulation has been reported in lung cancer, and overexpression correlates with worse prognosis in NSCLC patients. Most importantly, PKC isozymes have been established as mediators of resistance to tyrosine kinase inhibitors in NSCLC. Unfortunately, however, PKC-directed therapeutics have yielded unsatisfactory results, likely due to a lack of specific evaluation for PKC. To achieve satisfactory results in clinical trials, predictive biomarkers of PKC activity must be established and screened for prior to patient enrollment. Furthermore, tandem inhibition of PKC and molecular drivers may be a potential therapeutic strategy to prevent the emergence of resistance in NSCLC.

scholarly journals RNA-Based Assay for Next-Generation Sequencing of Clinically Relevant Gene Fusions in Non-Small Cell Lung Cancer

Cancers ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 139
Author(s):  
Caterina De Luca ◽  
Francesco Pepe ◽  
Antonino Iaccarino ◽  
Pasquale Pisapia ◽  
Luisella Righi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Limit Of Detection ◽  
Predictive Biomarkers ◽  
Small Cell ◽  
Clinical Samples ◽  
Gene Fusions ◽  
Small Cell Lung ◽  
Relevant Gene

Gene fusions represent novel predictive biomarkers for advanced non-small cell lung cancer (NSCLC). In this study, we validated a narrow NGS gene panel able to cover therapeutically-relevant gene fusions and splicing events in advanced-stage NSCLC patients. To this aim, we first assessed minimal complementary DNA (cDNA) input and the limit of detection (LoD) in different cell lines. Then, to evaluate the feasibility of applying our panel to routine clinical samples, we retrospectively selected archived lung adenocarcinoma histological and cytological (cell blocks) samples. Overall, our SiRe RNA fusion panel was able to detect all fusions and a splicing event harbored in a RNA pool diluted up to 2 ng/µL. It also successfully analyzed 46 (95.8%) out of 48 samples. Among these, 43 (93.5%) out of 46 samples reproduced the same results as those obtained with conventional techniques. Intriguingly, the three discordant results were confirmed by a CE-IVD automated real-time polymerase chain reaction (RT-PCR) analysis (Easy PGX platform, Diatech Pharmacogenetics, Jesi, Italy). Based on these findings, we conclude that our new SiRe RNA fusion panel is a valid and robust tool for the detection of clinically relevant gene fusions and splicing events in advanced NSCLC.

scholarly journals How patients being treated for non-small cell lung cancer value treatment benefit despite side effects

2021 ◽  
Author(s):  
Mona L. Martin ◽  
Julia Correll ◽  
Andrew Walding ◽  
Anna Rydén
Keyword(s):  
Lung Cancer ◽  
Side Effects ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Advanced Nsclc ◽  
Small Cell ◽  
Small Cell Lung ◽  
Treatment Benefit ◽  
Treatment Expectations ◽  
Treatment Benefits

Abstract Purpose To describe symptoms and side effects experienced by patients with advanced non-small cell lung cancer (NSCLC), assess how patients allocate sensations (i.e. symptoms or side effects) to either the disease or its treatment, and evaluate how patients balance side effects with treatment benefits. Methods Qualitative sub-studies were conducted as part of two clinical trials in patients treated for advanced NSCLC (AURA [NCT01802632]; ARCTIC [NCT02352948]). Results Interviews were conducted with 23 patients and 19 patients in the AURA and ARCTIC sub-studies, respectively. The most commonly experienced symptoms/side effects were respiratory (81% of patients), digestive (76%), pain and discomfort (76%), energy-related (71%), and sensory (62%). Patients identified a sensation as a treatment side effect if they had not experienced it before, if there was a temporal link between the sensation and receipt of treatment, and/or if their doctors consistently told or asked them about it in relation to side effects. Themes that emerged when patients talked about their cancer treatment and its side effects related to the serious nature of their advanced disease and their treatment expectations. Patients focused on treatment benefits, wanting a better quality of life, being hopeful, not really having a choice, and not thinking about side effects. Conclusions In these two qualitative sub-studies, patients with advanced NSCLC valued the benefits of their treatment regardless of side effects that they experienced. Patients weighed their options against the seriousness of their disease and expressed their willingness to tolerate their side effects in return for receiving continued treatment benefits.

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