The between Now and Then of Lung Cancer Chemotherapy and Immunotherapy

Visconti, Roberta; Morra, Francesco; Guggino, Gianluca; Celetti, Angela

doi:10.3390/ijms18071374

Cited by 47 publications

(40 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the contest of BReast CAncer gene (BRCA)-mutated cancers with compromised HR repair, low CCDC6 protein levels can increase lung cancers cells' sensitivity to olaparib alone or synergize with chemotherapy. On the other hand, these DNA damaging agents can also increase the immunogenicity of the tumor and possibly improve ICI efficacy [67,68].…”

Section: Discussionmentioning

confidence: 99%

EPSILoN: A Prognostic Score for Immunotherapy in Advanced Non-Small-Cell Lung Cancer: A Validation Cohort

Prelaj

Ferrara

Rebuzzi

et al. 2019

Cancers

View full text Add to dashboard Cite

Background: Beyond programmed death ligand 1 (PD-L1), no other biomarkers for immunotherapy are used in daily practice. We previously created EPSILoN (Eastern Cooperative Oncology Group performance status (ECOG PS), smoking, liver metastases, lactate dehydrogenase (LDH), neutrophil-to-lymphocyte ratio (NLR)) score, a clinical/biochemical prognostic score, in 154 patients treated with second/further-line immunotherapy. This study’s aim was to validate EPSILoN score in a different population group. Methods: 193 patients were included at National Cancer Institute of Milan (second-line immunotherapy, 61%; further-line immunotherapy, 39%). Clinical/laboratory parameters such as neutrophil-to-lymphocyte ratio and lactate dehydrogenase levels were collected. Kaplan–Meier and Cox hazard methods were used for survival analysis. Results: Overall median progression-free survival and median overall survival were 2.3 and 7.6 months, respectively. Multivariate analyses for Progression-Free Survival (PFS) identified heavy smokers (hazard ratio (HR) 0.71, p = 0.036) and baseline LDH < 400 mg/dL (HR 0.66, p = 0.026) as independent positive factors and liver metastases (HR 1.48, p = 0.04) and NLR ≥ 4 (HR 1.49, p = 0.029) as negative prognostic factors. These five factors were included in the EPSILoN score which was able to stratify patients in three different prognostic groups, high, intermediate and low, with PFS of 6.0, 3.8 and 1.9 months, respectively (HR 1.94, p < 0.001); high, intermediate and low prognostic groups had overall survival (OS) of 24.5, 8.9 and 3.4 months, respectively (HR 2.40, p < 0.001). Conclusions: EPSILoN, combining five baseline clinical/blood parameters (ECOG PS, smoking, liver metastases, LDH, NLR), may help to identify advanced non-small-cell lung cancer (aNSCLC) patients who most likely benefit from immune checkpoint inhibitors (ICIs).

show abstract

Section: Discussionmentioning

confidence: 99%

EPSILoN: A Prognostic Score for Immunotherapy in Advanced Non-Small-Cell Lung Cancer: A Validation Cohort

Prelaj

Ferrara

Rebuzzi

et al. 2019

Cancers

View full text Add to dashboard Cite

show abstract

“…In fact, the overall 5-year survival rate of NSCLC patients is still less than 20% [1]. Recently, emerging immunotherapies for this recurrent cancer have gained attention [3,4]. Differing from traditional therapies including chemotherapy, radiotherapy, and their combinations with angiogenesis inhibitors, immunotherapies primarily target the rapidly dividing tumor cells by affecting key molecular events that drive tumor cell growth and invasion.…”

Section: Introductionmentioning

confidence: 99%

Overexpressed D2 Dopamine Receptor Inhibits Non-Small Cell Lung Cancer Progression through Inhibiting NF-κB Signaling Pathway

Zhang

Deng

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Non-small cell lung cancer (NSCLC) is one of the deadliest cancers worldwide. Dopamine receptor D2 (DRD2) has multiple roles in clinical progression of NSCLC and functional maintenance of cancer cells. However, little is known about the molecular mechanism. Here, we clarified whether DRD2 inhibits lung cancer progression and identified the underlying downstream signaling. Methods: DRD2 mRNA and protein levels were detected in clinical specimens by qRT-PCR and immunohistochemistry, respectively. MTT and colony formation assays were applied to analyze cell proliferation. The underlying molecular mechanism was identified by dual luciferase, western blot, qRT-PCR, cAMP detection, immunoprecipitation, and chromatin immunoprecipitation assays. A murine NSCLC model was used to clarify the role of DRD2 in tumor cell proliferation. Results: We found that DRD2 ablated tumor cell growth. DRD2 expression in NSCLC tissues was lower than in adjacent normal lung tissues. Moreover, DRD2 mRNA and protein levels in NSCLC were negatively correlated with the tumor size, TNM status, and patient overall survival. In vitro experiments showed that disruption of DRD2 promoted the proliferation of NSCLC cell lines A549 and SK-MES-1 by inhibiting the NF-κB signaling pathway. Furthermore, DRD2 overexpression not only blocked lipopolysaccharide-induced A549 and SK-MES-1 cell proliferation and growth, but also inhibited the tumorigenesis in murine xenograft models. Conclusion: These results indicate that DRD2 may be a potential therapeutic target for lung cancer patients with high DRD2 expression by ablating the NF-κB signaling pathway.

show abstract

“…17,18 Inspired results from the clinical trials and clinical experience of immunotherapy with or without chemotherapy have significantly improved the outcome of lung cancer. 19 NCCN guidelines of lung cancer has recommended immunotherapy as the second-line drugs, even as the first choice for Stage IV patients with high expression of PD-1/PD-L1. 20 This sheds light on the significance of tumor microenvironment for the treatment and prognosis of LUAD.…”

Section: Discussionmentioning

confidence: 99%

Profiles of immune infiltration in lung adenocarcinoma and their clinical significant: A gene‐expression–based retrospective study

Chen

Dong

et al. 2020

J of Cellular Biochemistry

View full text Add to dashboard Cite

Lung cancer is one of the fatal tumors. The tumor microenvironment plays a key role in regulating tumor progression. To figure out the role of tumor microenvironment in lung adenocarcinoma (LUAD), ESTIMATE algorithm was used to evaluate the immune scores in LUAD. Patients with low immune scores had a worse overall survival (OS) compared with high immune scores. Using RNA‐Seq data of 489 patients in The Cancer Genome Atlas (TCGA), differentially expressed genes (DEGs) were identified between high‐ and low‐immune score groups. Based on the DEGs, nine‐gene signature was constructed by the least absolute shrinkage and selection operator Cox regression model in TCGA set. The signature demonstrated significant prognostic value in both TCGA and Gene Expression Omnibus database. Multivariate Cox regression analyses indicated that nine‐genes signature was an independent prognostic factor. Subgroup analysis also revealed a robust prognostic ability of nine‐gene signature. A nomogram with a C‐index of 0.722 had a favorable power for predicting 3‐, 5‐, and 10‐year survival for clinical use by integrating nine‐gene signature and other clinical features. Co‐expression and functional enrichment analysis showed that nine‐gene signature was significantly associated with immune response and provided potential profound molecules for revealing the mechanism of tumor initiation and progression. In conclusion, we revealed the significance of immune infiltration and built a novel nine‐gene signature as a reliable prognostic factor for patients with LUAD.

show abstract

The between Now and Then of Lung Cancer Chemotherapy and Immunotherapy

Cited by 47 publications

References 51 publications

EPSILoN: A Prognostic Score for Immunotherapy in Advanced Non-Small-Cell Lung Cancer: A Validation Cohort

EPSILoN: A Prognostic Score for Immunotherapy in Advanced Non-Small-Cell Lung Cancer: A Validation Cohort

Overexpressed D2 Dopamine Receptor Inhibits Non-Small Cell Lung Cancer Progression through Inhibiting NF-κB Signaling Pathway

Profiles of immune infiltration in lung adenocarcinoma and their clinical significant: A gene‐expression–based retrospective study

Contact Info

Product

Resources

About